Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 46...Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.展开更多
Background Screening and pre-symptomatic diagnosis in newborns allows early treatment of thalassemia and abnormal hemoglobin(Hb)disorders in childhood.However,there remains a lack of efficient methods to screen for he...Background Screening and pre-symptomatic diagnosis in newborns allows early treatment of thalassemia and abnormal hemoglobin(Hb)disorders in childhood.However,there remains a lack of efficient methods to screen for hemoglobinopathies in newborns.This study aimed to establish a bottom-up mass spectrometry(MS)-based method for efficient screening of hemoglobinopathies in newborns using dried blood spot(DBS)samples.Methods We developed LC-MS methodology using high-performance liquid chromatography(HPLC)combined with highresolution mass spectrometry(HRMS).DBS samples from patients covering the most common types of hemoglobinopathies and normal controls were collected.We extracted Hb from a 3.2 mm disc punched from the DBS sample,which was then digested with trypsin to release a series of Hb-specific peptides.Using HPLC-HRMS,we identified disease-related peptides for biomarker design.Using this methodology,we built a prediction model using binary logistic regression to facilitate efficient screening.Results This new method costs less than$1 per test and can process at least 192 samples per batch.Our methodology is fast with a sampling and analysis time of 2.6 minutes and inter-and intra-assay coefficients of variation below 14.67%.Moreover,we report low limits of quantification for the proteo-specific peptides(0.50-60.00μg/L).No significant matrix effects or carryover were observed.Our method could give reliable results even with DBS samples stored for one month.Prospective application of this method to 2726 newborns identified 87 patients with hemoglobinopathies and achieved high screening sensitivity and specificity for deletionalα-thalassemia(--^(SEA))(100.00%and 100.00%),β-thalassemia(97.50%and 89.63%)and other abnormal Hb disorders.Conclusions We have developed a low-cost,high-throughput method for reliable screening of thalassemia and abnormal Hb disorders in newborns.This could be deployed as a first-line screening test.展开更多
Background Data of classical inborn errors of metabolism （IEM） of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IE...Background Data of classical inborn errors of metabolism （IEM） of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.展开更多
Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn disease...Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.展开更多
Background It has been 11 years since newborn screening started in Zhejiang in 1999.The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009.Methods Blood sample...Background It has been 11 years since newborn screening started in Zhejiang in 1999.The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009.Methods Blood samples were collected from the heels of newborns 72 hours after birth.We have conducted laboratory tests that the congenital hypothyroidism （CH） and circulating levels of thyroid-stimulating hormone （TSH） was detected.Blood phenylalanine （Phe） was detected for phenylketonuria （PKU）.Dissociation-enhanced lanthanide fluorescent immunoassay （DELFIA） was used for detection.Results From 1999 to 2009,3875228 newborns were screened and 2309 cases were confirmed as CH and 155 cases were confirmed as PKU.The incidence of CH and PKU were 1：1678 and 1：25 001 respectively.Conclusion In 11 years,the Zhejiang newborn screening center screened more than 3.8 million newboms,and helped more than 2000 CH and PKU patients to obtain early treatment in order to prevent physical disability and mental retardation.展开更多
Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucas...Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.展开更多
Newborn screening(NBS)is a public health service aimed at identifying infants with severe genetic disorders,thus providing effective treatment early enough to prevent or ameliorate the onset of symptoms.Current NBS us...Newborn screening(NBS)is a public health service aimed at identifying infants with severe genetic disorders,thus providing effective treatment early enough to prevent or ameliorate the onset of symptoms.Current NBS uses biochemical analysis of dried blood spots,predominately with timeresolved fluorescence immunoassay and tandem mass spectrometry,which produces some false positives and false negatives.The application of enzymatic activity-based testing technology provides a reliable screening method for some disorders.Genetic testing is now commonly used for secondary or confirmatory testing after a positive result in some NBS programs.Recently,next-generation sequencing(NGS)has emerged as a robust tool that enables large panels of genes to be scanned together rapidly.Rapid advances in NGS emphasize the potential for genomic sequencing to improve NBS programs.However,some challenges still remain and require solution before this is applied for population screening.展开更多
Background:Galactosemia due to complete or near-complete galactose-l-phosphate uridyltransferase(GALT)deficiency was the first disorder added to the pioneering newborn screening panel besides phenylketonuria.In the la...Background:Galactosemia due to complete or near-complete galactose-l-phosphate uridyltransferase(GALT)deficiency was the first disorder added to the pioneering newborn screening panel besides phenylketonuria.In the last 50 years,many criticisms have been focused on the opportunity of its inclusion.Consequently,long-term single center experiences with this issue are generally lacking.Methods:We reviewed the outcome of newborn screening for hypergalactosemia performed at our department since 1982 and the correspondent long-term clinical outcome.Results:Among 1123909 newborns screened for hypergalactosemia,33 showed abnormal results confirmed at second tier test.Thirteen patients were affected with classic galactosemia,8 partial GALT deficiency,3 severe galactokinase deficiency,7 transient galactosemia,one congenital porto-systemic shunt,and one glucose transporter 2 deficiency.Acute neonatal liver failure in the late first week of life(5.8±1.1 days)unavoidably complicated the clinical course of classic galactosemia,unless in three second-born siblings treated on the basis of presumptive diagnosis immediately after newborn screening sample collection on day 3.Despite early treatment and longterm steadily normal peripheral blood galactose,77%of patients with severe GALT deficiency present mild to severe intellectual disabilities.All patients with partial GALT deficiency showed normal intellectual development on a regular diet,as well as patients with galactokinase deficiency under treatment.Conclusions:Availability of screening results within the fifth day after birth would allow the prevention of acute decompensation in classic galactosemia.A systematic diagnostic work-up in all positive newborns is essential to unravel the etiology of hypergalactosemia.展开更多
Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outco...Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outcomes.Advances in real-time polymerase chain reaction(PCR)technology have been instrumental in facilitating their inclusion in NBS programs.Methods We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles(TRECs),kappadeleting recombination excision circles(KRECs),and the absence of the survival motor neuron(SMN)1 gene in dried blood spots from 103,240 newborns in Zhejiang Province,China,between July 2021 and December 2022.Results Of all the samples,122 were requested further evaluation.After fow cytometry evaluation and/or genetic diagnostics,we identifed one patient with SCID,two patients with XLA,nine patients with SMA[one of whom also had Wiskott–Aldrich Syndrome(WAS)],and eight patients with other medical conditions.The positive predictive values(PPVs)of NBS for SCID,XLA,and SMA were 2.44%,2.78%,and 100%,respectively.The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID,1 in 51,620 for XLA,and 1 in 11,471 for SMA.Conclusion This study represents the frst large-scale screening in China's Mainland using a TREC/KREC/SMN1 multiplex assay,providing valuable epidemiological data.Our fndings suggest that this multiplex assay is an efective screening method for SCID,XLA,and SMA,potentially supporting the universal implementation of NBS programs across China.展开更多
Newborn hearing screening is an effective strategy for early identification of hearing loss in the newborn which result in early intervention and best outcome.However implementing universal screening strategy is a cha...Newborn hearing screening is an effective strategy for early identification of hearing loss in the newborn which result in early intervention and best outcome.However implementing universal screening strategy is a challenge in many resource constrained settings.There are various limitations towards successful implementation of hearing screening program in the developing countries.The cost effectiveness of the screening program also needs to be considered in a resource constrained settings.We attempt to provide a viewpoint that can be potentially helpful for the successful implementation of hearing screening in a resource constrained settings of the developing countries.展开更多
Direct infusion mass spectrometry(DIMS) is a powerful technique in clinical diagnosis for screening neonatal amino acid metabolic disorders from dried blood spots(DBS).However,DIMS sometimes generated false-positive r...Direct infusion mass spectrometry(DIMS) is a powerful technique in clinical diagnosis for screening neonatal amino acid metabolic disorders from dried blood spots(DBS).However,DIMS sometimes generated false-positive results for analysis of amino acids.In this work,we utilized a stable isotope derivatization method,combining with liquid chromatography tandem mass spectrometry(SID-LC-MS),to improve the specificity for screening amino acids in DBS specimens.A pair of isotope reagents,p-(dimethylamino)phenyl isothiocyanate(DMAP-NCS) and 4-isothiocyanato-N,N-bis(methyl-[2H2])aniline([2H4]DMAP-NCS),was synthesized and used to label amino acids in DBS specimens.The [2H4]DMAP-NCS labelled amino acid standards were used as internal standards to compensate the matrix effect.This method was validated by measuring linearity,recovery and accuracy.The results showed that the developed SID-LC-MS method can be used for sensitive and selective determination of 12 diagnostically important amino acids in DBS specimens.展开更多
Vitamin B 12 deficiency,mostly of maternal origin in newborns,is a well treatable condition but can cause severe neurologic sequelae.In women of childbearing age and pregnant women worldwide vitamin B12 deficiency has...Vitamin B 12 deficiency,mostly of maternal origin in newborns,is a well treatable condition but can cause severe neurologic sequelae.In women of childbearing age and pregnant women worldwide vitamin B12 deficiency has been reported with frequencies of 10%-50%.Children with vitam in B I2 deficiency are asym ptom atic at birth but may develop severe multisystemic symptoms,including irreversible developmental impairment in the second halfyear of life.Early detection of vitamin B12 deficiency allows for presymptomatic treatment.This article provides an overview over the function of vitamin B12 and discusses causes and frequency of vitamin B12 deficiency in newborns,infants,and women of childbearing age.It describes novel successful approaches to newborn screening(NBS)for vitamin B,2 deficiency and results of a pilot study which performed systematic NBS for vitamin B12 deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots.Recommendations for diagnostics in mothers of children with vitamin B12 deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B12 deficiency detected by NBS.Treatment options of vitamin B12 deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin BI2 supplementation.Recommendations for preventive approaches to vitamin Bl2 deficiency for children and mothers are stated.Many children worldwide could benefit from systematic inclusion of vitamin B12 deficiency into NBS panels.In addition,preventive approaches to maternal vitamin B12 deficiency should be implemented systematically during maternal care.展开更多
Hemoglobinopathies, mainly Sickle cell disease (SCD), are the most common monogenic disorders in Africa. In Burkina Faso, data on these diseases are scarce, mainly hospital-based in Ouagadougou and its surroundings. I...Hemoglobinopathies, mainly Sickle cell disease (SCD), are the most common monogenic disorders in Africa. In Burkina Faso, data on these diseases are scarce, mainly hospital-based in Ouagadougou and its surroundings. In order to assess the incidence and allelic frequencies of the main hemoglobinopathies in newborns in Burkina Faso, we conducted a cross-sectional study from 2015 to 2019 in four hospitals. The study included babies of both sexes, regardless of ethnic group and parents’ hemoglobin status. It was a newborn screening and hemoglobin variants were detected using isoelectric focusing on cord blood samples and confirmed using hemoglobin electrophoresis by high-performance liquid chromatography. The proportions and cumulative incidences of the different hemoglobinopathies were computed. Hardy-Weinberg equilibrium law was applied to calculate genotypic and allelic frequencies. The significant level was p < 0.05. Out of 11,337 newborns included, 47.8% were males and 60.2% were from Bobo-Dioulasso. Abnormal hemoglobin was found in 27.1%, representing a cumulative incidence of 1:4 newborns. The incidence of SCD was 1.9% (1:53 newborns) with 27.9% of homozygous SS. Homozygous CC and compound heterozygous Cβ-Thalassemia accounted for 1.1%. SCD cases were 1.51 times higher in Bobo-Dioulasso (OR = 1.51;95% CI [1.09 - 2.10]: p = 0.013). The observed genotype frequencies were significantly different from the expected ones (p 0.001). The βS and βC alleles represented 5.1 and 9.9%, respectively. This study showed a high incidence of hemoglobinopathies. Such results raise the question of control strategies for these hemoglobinopathies in our country.展开更多
Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented....Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented.This consensus,developed by multidisciplinary experts,aims to standardize the combined screening of genes and biomarkers for neonatal diseases in China,balancing ethical,technical,and clinical considerations.Data sources This consensus synthesizes evidence from peer-reviewed literature(PubMed,CNKI,etc.)up to 2024 and integrates clinical experiences from multidisciplinary experts in neonatology,genetics,and laboratory medicine,focusing on disease biomarker-based NBS,newborn genetic screening,and the clinical utility of combined screening.Results The consensus defines principles for combined screening:(1)disease/gene selection:154 disease-causing genes covering 67 inherited metabolic disorders(e.g.,amino acid metabolism disorders,organic acid metabolism disorders),prioritized by treatability,onset age(<5 years),and cost-effectiveness;(2)methodology:integrating dried blood spot biomarker analysis with next-generation sequencing-based targeted capture(coverage>300×),validated by MLPA/Sanger and longrange sequencing for complex variants(e.g.,CYP21A2,SLC25A13);and(3)operational workflow:standardized workflows for informed consent,sample collection/delivery,and result interpretation,with dual reporting of marker and genetic findings within 15 days.Positive cases require family verification and/or other genetic sequencing techniques.Conclusions This consensus establishes a practical framework for integrating marker and genetic screening,aiming to improve diagnostic accuracy and achieve rapid and effective interventions,thereby saving lives and reducing the occurrence of severe complications.Implementation requires interdisciplinary collaboration and ongoing quality control to maximize clinical utility.展开更多
Universal newborn hearing screening(UNHS)is recognized as the most effective strategy for early detection of congenital hearing loss;however,screening coverage remains inadequate in many countries.In China,newborn hea...Universal newborn hearing screening(UNHS)is recognized as the most effective strategy for early detection of congenital hearing loss;however,screening coverage remains inadequate in many countries.In China,newborn hearing screening has been implemented for over two decades.To evaluate our policies and practices during this period and assess resource equity,health impacts,and future challenges,we conducted a nationwide survey focusing on newborn hearing screening coverage,the number of special schools for deaf-mutes,and the proportion of hearing-impaired students in mainstream education.From 2001 to 2020,China’s UNHS program coverage increased from 10.9%to 94.3%,while the proportion of hearing-impaired students in mainstream education rose from 24.8%to 57.5%.Concurrently,the number of hearing-impaired students in special schools decreased from 76,554 to 34,945,and the number of special schools for deaf-mutes declined from 639 to 389.Through the implementation of the UNHS program,China has made substantial progress in improving newborn hearing health,yielding long-term benefits for those with congenital hearing loss.However,targeted resource allocation and the establishment of a national platform remain priorities for future development.Our experience may provide valuable insights for similar settings.展开更多
Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the ...Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.展开更多
Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell l...Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.展开更多
Glutaric acidemia type Ⅱ （GAⅡ）, also known as multiple acyl-CoA dehydrogenase defciency, is an auto-somal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electro...Glutaric acidemia type Ⅱ （GAⅡ）, also known as multiple acyl-CoA dehydrogenase defciency, is an auto-somal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electron transfer flavoprotein （ETF）-A mutations in a 2-year-old female with thalassemia minor. The patient developed an episode of hypoglycemia and hypotonicityon the postnatal first day. Laboratory investigations revealed elevations of multiple acyl carnitines indicat-ing glutaric acidemia type Ⅱ in newborn screening analysis. Urinary organic acids were evaluated for the confrmation and revealed a high glutaric acid excretion. Genetic analysis revealed two novel mutations in the ETF-A gene, which are considered to be compound heterozygote. At the 8 mo of life ketone therapy was added, which significantly increased the neuromotor development. The patient had been closely followed for two years with carnitine, ribofavin, coenzyme Q10, and ketone supplementation in addition to a high carbohydrate diet. Although the patient had comorbidity like thalassemia minor, her neuromotor developmentwas normal for her age and had no major health problems. This specific case expands the previously reported spectrum of this disease.展开更多
Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited dis...Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.展开更多
Background: Cochlear implantation is the best management option for children with profound hearing loss and has received no benefit from hearing aids. Early implantation for these children is associated with good spee...Background: Cochlear implantation is the best management option for children with profound hearing loss and has received no benefit from hearing aids. Early implantation for these children is associated with good speech and language outcomes. Objectives: To determine the barriers to early pediatric cochlear implantation. Methodology: A qualitative cross-sectional study was conducted at Hearing Implants Centre in Nairobi Kenya from August 2022 to February 2023. The target population was 40 children who had undergone cochlear implantation under the auspices of Cochlear Implant Group of Kenya but data was only collected from 30 of them. The remaining were ruled out because 3 were unreachable over the phone, 5 refused to participate and 2 did not meet the inclusion criteria. Results: Patient file reviews and parental telephone interviews were conducted to collect information and analyzed using Microsoft excel and presented using graphs, tables and pie charts. The analysis of the gender showed 46.67% were male and 53.33% were female. Analysis on newborn screening showed that none had it done. The mode age of hearing loss suspicion was between the ages of 2 - 3 years. The hearing loss suspicion done was done by the mothers at 20 children the reminder being 3 by the father, 1 by a family friend, 4 by the school-teacher and 2 by the child’s grandmother. A total of 17 participants noted a delayed in speech and language, 9 noted that the child did not respond to loud sounds, 4 noted that the children did not turn when called. Once hearing loss was identified, 73% saw the ENT, 17% saw a pediatrician, 7% went to see an Audiologist, and 3% saw a speech therapist. The mode age at diagnosis was 1.5 years. The mode age at implantation was 5 years. The mode time from diagnosis was 2 years. Conclusions: This study sought to investigate the barriers to pediatric cochlear implantation in Kenya. From the results it was determined that factors such as lack of newborn screening, high cost of cochlear implantation, lack of awareness have led to late cochlear implantation.展开更多
基金partially supported by grants from the Ministry of Science and Technology of China(2016YFC1000306)the Beijing Municipal Science and Technology Commission Foundation(Z181100001918003)+1 种基金the Beijing Municipal Commission of Health and Family Planning Foundation(2018-21141,2020-4-1144)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201905)。
文摘Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.
基金supported by the Natural Science Foundation Project of Chongqing(cstc2021jcyj-msxmX0003)Joint project of Chongqing Health Commission and Science and Technology Bureau(2025MSXM031)Chongqing Fuling District Science and Health Joint Medical Scientific research Project(2023KWLH010).
文摘Background Screening and pre-symptomatic diagnosis in newborns allows early treatment of thalassemia and abnormal hemoglobin(Hb)disorders in childhood.However,there remains a lack of efficient methods to screen for hemoglobinopathies in newborns.This study aimed to establish a bottom-up mass spectrometry(MS)-based method for efficient screening of hemoglobinopathies in newborns using dried blood spot(DBS)samples.Methods We developed LC-MS methodology using high-performance liquid chromatography(HPLC)combined with highresolution mass spectrometry(HRMS).DBS samples from patients covering the most common types of hemoglobinopathies and normal controls were collected.We extracted Hb from a 3.2 mm disc punched from the DBS sample,which was then digested with trypsin to release a series of Hb-specific peptides.Using HPLC-HRMS,we identified disease-related peptides for biomarker design.Using this methodology,we built a prediction model using binary logistic regression to facilitate efficient screening.Results This new method costs less than$1 per test and can process at least 192 samples per batch.Our methodology is fast with a sampling and analysis time of 2.6 minutes and inter-and intra-assay coefficients of variation below 14.67%.Moreover,we report low limits of quantification for the proteo-specific peptides(0.50-60.00μg/L).No significant matrix effects or carryover were observed.Our method could give reliable results even with DBS samples stored for one month.Prospective application of this method to 2726 newborns identified 87 patients with hemoglobinopathies and achieved high screening sensitivity and specificity for deletionalα-thalassemia(--^(SEA))(100.00%and 100.00%),β-thalassemia(97.50%and 89.63%)and other abnormal Hb disorders.Conclusions We have developed a low-cost,high-throughput method for reliable screening of thalassemia and abnormal Hb disorders in newborns.This could be deployed as a first-line screening test.
文摘Background Data of classical inborn errors of metabolism （IEM） of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.
基金the Foundation of National Key R&D Program of China of Research on Application Demonstration and Evaluation of Comprehensive Prevention And Control Technology of Birth Defects(Grant No.2018YFC1002700)Zhejiang R&D Research Project Research on New Technologies for Birth Health,Birth Safety and Perinatal Disease Diagnosis and Treatment(Grant No.2021C03099).
文摘Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.
文摘Background It has been 11 years since newborn screening started in Zhejiang in 1999.The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009.Methods Blood samples were collected from the heels of newborns 72 hours after birth.We have conducted laboratory tests that the congenital hypothyroidism （CH） and circulating levels of thyroid-stimulating hormone （TSH） was detected.Blood phenylalanine （Phe） was detected for phenylketonuria （PKU）.Dissociation-enhanced lanthanide fluorescent immunoassay （DELFIA） was used for detection.Results From 1999 to 2009,3875228 newborns were screened and 2309 cases were confirmed as CH and 155 cases were confirmed as PKU.The incidence of CH and PKU were 1：1678 and 1：25 001 respectively.Conclusion In 11 years,the Zhejiang newborn screening center screened more than 3.8 million newboms,and helped more than 2000 CH and PKU patients to obtain early treatment in order to prevent physical disability and mental retardation.
文摘Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.
文摘Newborn screening(NBS)is a public health service aimed at identifying infants with severe genetic disorders,thus providing effective treatment early enough to prevent or ameliorate the onset of symptoms.Current NBS uses biochemical analysis of dried blood spots,predominately with timeresolved fluorescence immunoassay and tandem mass spectrometry,which produces some false positives and false negatives.The application of enzymatic activity-based testing technology provides a reliable screening method for some disorders.Genetic testing is now commonly used for secondary or confirmatory testing after a positive result in some NBS programs.Recently,next-generation sequencing(NGS)has emerged as a robust tool that enables large panels of genes to be scanned together rapidly.Rapid advances in NGS emphasize the potential for genomic sequencing to improve NBS programs.However,some challenges still remain and require solution before this is applied for population screening.
文摘Background:Galactosemia due to complete or near-complete galactose-l-phosphate uridyltransferase(GALT)deficiency was the first disorder added to the pioneering newborn screening panel besides phenylketonuria.In the last 50 years,many criticisms have been focused on the opportunity of its inclusion.Consequently,long-term single center experiences with this issue are generally lacking.Methods:We reviewed the outcome of newborn screening for hypergalactosemia performed at our department since 1982 and the correspondent long-term clinical outcome.Results:Among 1123909 newborns screened for hypergalactosemia,33 showed abnormal results confirmed at second tier test.Thirteen patients were affected with classic galactosemia,8 partial GALT deficiency,3 severe galactokinase deficiency,7 transient galactosemia,one congenital porto-systemic shunt,and one glucose transporter 2 deficiency.Acute neonatal liver failure in the late first week of life(5.8±1.1 days)unavoidably complicated the clinical course of classic galactosemia,unless in three second-born siblings treated on the basis of presumptive diagnosis immediately after newborn screening sample collection on day 3.Despite early treatment and longterm steadily normal peripheral blood galactose,77%of patients with severe GALT deficiency present mild to severe intellectual disabilities.All patients with partial GALT deficiency showed normal intellectual development on a regular diet,as well as patients with galactokinase deficiency under treatment.Conclusions:Availability of screening results within the fifth day after birth would allow the prevention of acute decompensation in classic galactosemia.A systematic diagnostic work-up in all positive newborns is essential to unravel the etiology of hypergalactosemia.
基金sponsored by the National Key Research and Development Program of China(No.2022YFC2703401).
文摘Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outcomes.Advances in real-time polymerase chain reaction(PCR)technology have been instrumental in facilitating their inclusion in NBS programs.Methods We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles(TRECs),kappadeleting recombination excision circles(KRECs),and the absence of the survival motor neuron(SMN)1 gene in dried blood spots from 103,240 newborns in Zhejiang Province,China,between July 2021 and December 2022.Results Of all the samples,122 were requested further evaluation.After fow cytometry evaluation and/or genetic diagnostics,we identifed one patient with SCID,two patients with XLA,nine patients with SMA[one of whom also had Wiskott–Aldrich Syndrome(WAS)],and eight patients with other medical conditions.The positive predictive values(PPVs)of NBS for SCID,XLA,and SMA were 2.44%,2.78%,and 100%,respectively.The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID,1 in 51,620 for XLA,and 1 in 11,471 for SMA.Conclusion This study represents the frst large-scale screening in China's Mainland using a TREC/KREC/SMN1 multiplex assay,providing valuable epidemiological data.Our fndings suggest that this multiplex assay is an efective screening method for SCID,XLA,and SMA,potentially supporting the universal implementation of NBS programs across China.
文摘Newborn hearing screening is an effective strategy for early identification of hearing loss in the newborn which result in early intervention and best outcome.However implementing universal screening strategy is a challenge in many resource constrained settings.There are various limitations towards successful implementation of hearing screening program in the developing countries.The cost effectiveness of the screening program also needs to be considered in a resource constrained settings.We attempt to provide a viewpoint that can be potentially helpful for the successful implementation of hearing screening in a resource constrained settings of the developing countries.
基金supported by the National Key R&D Program of China(No.2018YFA0900400)the National Natural ScienceFoundation of China(Nos.21635006,31670373,21721005,21904099)the Postdoctoral Science Foundation of China(No.2018M642893)。
文摘Direct infusion mass spectrometry(DIMS) is a powerful technique in clinical diagnosis for screening neonatal amino acid metabolic disorders from dried blood spots(DBS).However,DIMS sometimes generated false-positive results for analysis of amino acids.In this work,we utilized a stable isotope derivatization method,combining with liquid chromatography tandem mass spectrometry(SID-LC-MS),to improve the specificity for screening amino acids in DBS specimens.A pair of isotope reagents,p-(dimethylamino)phenyl isothiocyanate(DMAP-NCS) and 4-isothiocyanato-N,N-bis(methyl-[2H2])aniline([2H4]DMAP-NCS),was synthesized and used to label amino acids in DBS specimens.The [2H4]DMAP-NCS labelled amino acid standards were used as internal standards to compensate the matrix effect.This method was validated by measuring linearity,recovery and accuracy.The results showed that the developed SID-LC-MS method can be used for sensitive and selective determination of 12 diagnostically important amino acids in DBS specimens.
文摘Vitamin B 12 deficiency,mostly of maternal origin in newborns,is a well treatable condition but can cause severe neurologic sequelae.In women of childbearing age and pregnant women worldwide vitamin B12 deficiency has been reported with frequencies of 10%-50%.Children with vitam in B I2 deficiency are asym ptom atic at birth but may develop severe multisystemic symptoms,including irreversible developmental impairment in the second halfyear of life.Early detection of vitamin B12 deficiency allows for presymptomatic treatment.This article provides an overview over the function of vitamin B12 and discusses causes and frequency of vitamin B12 deficiency in newborns,infants,and women of childbearing age.It describes novel successful approaches to newborn screening(NBS)for vitamin B,2 deficiency and results of a pilot study which performed systematic NBS for vitamin B12 deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots.Recommendations for diagnostics in mothers of children with vitamin B12 deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B12 deficiency detected by NBS.Treatment options of vitamin B12 deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin BI2 supplementation.Recommendations for preventive approaches to vitamin Bl2 deficiency for children and mothers are stated.Many children worldwide could benefit from systematic inclusion of vitamin B12 deficiency into NBS panels.In addition,preventive approaches to maternal vitamin B12 deficiency should be implemented systematically during maternal care.
文摘Hemoglobinopathies, mainly Sickle cell disease (SCD), are the most common monogenic disorders in Africa. In Burkina Faso, data on these diseases are scarce, mainly hospital-based in Ouagadougou and its surroundings. In order to assess the incidence and allelic frequencies of the main hemoglobinopathies in newborns in Burkina Faso, we conducted a cross-sectional study from 2015 to 2019 in four hospitals. The study included babies of both sexes, regardless of ethnic group and parents’ hemoglobin status. It was a newborn screening and hemoglobin variants were detected using isoelectric focusing on cord blood samples and confirmed using hemoglobin electrophoresis by high-performance liquid chromatography. The proportions and cumulative incidences of the different hemoglobinopathies were computed. Hardy-Weinberg equilibrium law was applied to calculate genotypic and allelic frequencies. The significant level was p < 0.05. Out of 11,337 newborns included, 47.8% were males and 60.2% were from Bobo-Dioulasso. Abnormal hemoglobin was found in 27.1%, representing a cumulative incidence of 1:4 newborns. The incidence of SCD was 1.9% (1:53 newborns) with 27.9% of homozygous SS. Homozygous CC and compound heterozygous Cβ-Thalassemia accounted for 1.1%. SCD cases were 1.51 times higher in Bobo-Dioulasso (OR = 1.51;95% CI [1.09 - 2.10]: p = 0.013). The observed genotype frequencies were significantly different from the expected ones (p 0.001). The βS and βC alleles represented 5.1 and 9.9%, respectively. This study showed a high incidence of hemoglobinopathies. Such results raise the question of control strategies for these hemoglobinopathies in our country.
基金supported by grants from the"Pioneer"and"Leading Goose"R&D Program of Zhejiang Province(No.2024C03152 to H.F.).
文摘Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented.This consensus,developed by multidisciplinary experts,aims to standardize the combined screening of genes and biomarkers for neonatal diseases in China,balancing ethical,technical,and clinical considerations.Data sources This consensus synthesizes evidence from peer-reviewed literature(PubMed,CNKI,etc.)up to 2024 and integrates clinical experiences from multidisciplinary experts in neonatology,genetics,and laboratory medicine,focusing on disease biomarker-based NBS,newborn genetic screening,and the clinical utility of combined screening.Results The consensus defines principles for combined screening:(1)disease/gene selection:154 disease-causing genes covering 67 inherited metabolic disorders(e.g.,amino acid metabolism disorders,organic acid metabolism disorders),prioritized by treatability,onset age(<5 years),and cost-effectiveness;(2)methodology:integrating dried blood spot biomarker analysis with next-generation sequencing-based targeted capture(coverage>300×),validated by MLPA/Sanger and longrange sequencing for complex variants(e.g.,CYP21A2,SLC25A13);and(3)operational workflow:standardized workflows for informed consent,sample collection/delivery,and result interpretation,with dual reporting of marker and genetic findings within 15 days.Positive cases require family verification and/or other genetic sequencing techniques.Conclusions This consensus establishes a practical framework for integrating marker and genetic screening,aiming to improve diagnostic accuracy and achieve rapid and effective interventions,thereby saving lives and reducing the occurrence of severe complications.Implementation requires interdisciplinary collaboration and ongoing quality control to maximize clinical utility.
基金Supported by National Natural Science Foundation of China(81730028,82371141,81800899)Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases Grant(14DZ2260300)+6 种基金Collaborative Innovation Project of Translational Medicine from Shanghai Jiao Tong University School of Medicine(TM202011)Shanghai Key Clinical Discipline(shlczdzk00802)Clinical Research Plan of SHDC(SHDC2020CR1044B)Biobank program of Shanghai ninth people’s hospital,Shanghai Jiao Tong University School of Medicine(YBKA202205)Clinical Research Program of Shanghai Municipal Health Commission Health(202240003)Shanghai Natural Science Foundation(23ZR1437100)Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong university School of Medicine(JYZZ260).
文摘Universal newborn hearing screening(UNHS)is recognized as the most effective strategy for early detection of congenital hearing loss;however,screening coverage remains inadequate in many countries.In China,newborn hearing screening has been implemented for over two decades.To evaluate our policies and practices during this period and assess resource equity,health impacts,and future challenges,we conducted a nationwide survey focusing on newborn hearing screening coverage,the number of special schools for deaf-mutes,and the proportion of hearing-impaired students in mainstream education.From 2001 to 2020,China’s UNHS program coverage increased from 10.9%to 94.3%,while the proportion of hearing-impaired students in mainstream education rose from 24.8%to 57.5%.Concurrently,the number of hearing-impaired students in special schools decreased from 76,554 to 34,945,and the number of special schools for deaf-mutes declined from 639 to 389.Through the implementation of the UNHS program,China has made substantial progress in improving newborn hearing health,yielding long-term benefits for those with congenital hearing loss.However,targeted resource allocation and the establishment of a national platform remain priorities for future development.Our experience may provide valuable insights for similar settings.
文摘Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.
文摘Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.
文摘Glutaric acidemia type Ⅱ （GAⅡ）, also known as multiple acyl-CoA dehydrogenase defciency, is an auto-somal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electron transfer flavoprotein （ETF）-A mutations in a 2-year-old female with thalassemia minor. The patient developed an episode of hypoglycemia and hypotonicityon the postnatal first day. Laboratory investigations revealed elevations of multiple acyl carnitines indicat-ing glutaric acidemia type Ⅱ in newborn screening analysis. Urinary organic acids were evaluated for the confrmation and revealed a high glutaric acid excretion. Genetic analysis revealed two novel mutations in the ETF-A gene, which are considered to be compound heterozygote. At the 8 mo of life ketone therapy was added, which significantly increased the neuromotor development. The patient had been closely followed for two years with carnitine, ribofavin, coenzyme Q10, and ketone supplementation in addition to a high carbohydrate diet. Although the patient had comorbidity like thalassemia minor, her neuromotor developmentwas normal for her age and had no major health problems. This specific case expands the previously reported spectrum of this disease.
文摘Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.
文摘Background: Cochlear implantation is the best management option for children with profound hearing loss and has received no benefit from hearing aids. Early implantation for these children is associated with good speech and language outcomes. Objectives: To determine the barriers to early pediatric cochlear implantation. Methodology: A qualitative cross-sectional study was conducted at Hearing Implants Centre in Nairobi Kenya from August 2022 to February 2023. The target population was 40 children who had undergone cochlear implantation under the auspices of Cochlear Implant Group of Kenya but data was only collected from 30 of them. The remaining were ruled out because 3 were unreachable over the phone, 5 refused to participate and 2 did not meet the inclusion criteria. Results: Patient file reviews and parental telephone interviews were conducted to collect information and analyzed using Microsoft excel and presented using graphs, tables and pie charts. The analysis of the gender showed 46.67% were male and 53.33% were female. Analysis on newborn screening showed that none had it done. The mode age of hearing loss suspicion was between the ages of 2 - 3 years. The hearing loss suspicion done was done by the mothers at 20 children the reminder being 3 by the father, 1 by a family friend, 4 by the school-teacher and 2 by the child’s grandmother. A total of 17 participants noted a delayed in speech and language, 9 noted that the child did not respond to loud sounds, 4 noted that the children did not turn when called. Once hearing loss was identified, 73% saw the ENT, 17% saw a pediatrician, 7% went to see an Audiologist, and 3% saw a speech therapist. The mode age at diagnosis was 1.5 years. The mode age at implantation was 5 years. The mode time from diagnosis was 2 years. Conclusions: This study sought to investigate the barriers to pediatric cochlear implantation in Kenya. From the results it was determined that factors such as lack of newborn screening, high cost of cochlear implantation, lack of awareness have led to late cochlear implantation.
