To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to ...To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening （UNHS） were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn＇t pass the heating screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit （NICU）, neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity （OR=16.285, 95% CI 3.379--78,481）, neonatal disease （OR=34;968, 95% CI 2.720 449.534）, family history of congenital hearing loss （OR=69.488, 95% CI 4.417--1093.300） and birth weight （OR=0.241, 95% CI 0.090--0.648）. It is concluded that parity, neonatal disease and family history of heating loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.展开更多
BACKGROUND Acephalic spermatozoa syndrome(ASS)is an extremely rare form of severe teratozoospermia,where in most of the sperm either appear to lack heads or have disconnected or poorly connected heads and tails.CASE S...BACKGROUND Acephalic spermatozoa syndrome(ASS)is an extremely rare form of severe teratozoospermia,where in most of the sperm either appear to lack heads or have disconnected or poorly connected heads and tails.CASE SUMMARY We reported the case of a male patient with secondary infertility whose sperm showed typical ASS upon morphological analysis.Whole-exome sequencing was performed on the patient’s peripheral blood,which revealed two heterozygous variants of the PMFBP1 gene:PMFBP1c.414+1G>T(p.?)and PMFBP1c.393del(p.C132Afs*3).CONCLUSION It is speculated that the compound homozygous mutation of PMFBP1 may be the cause of ASS.We conducted a literature review in order to provide the basis for genetic counseling and clinical diagnosis of patients with ASS.展开更多
This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the &...This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the 'March of Dimes Global Network for Maternal and Infant Health(GNMIH)' ,allows developing country experts to more easily share their knowledge,experience,skills and materials in ways that can improve women's,maternal,newborn and child health in lower-income countries. This report begins with a brief description of the March of Dimes and its Global Programs which oversees the GNMIH. It then discusses the structure of the GNMIH,with an emphasis on the benefits and challenges of working within the network,and concludes with a brief description of the acti-vities of network members.展开更多
Most newborn screening laboratories use CE-marked or FDA-approved test-kits, like in routine clinical chemistry. National regulations require only minimal evaluation from the customer, if the test-kits are used as spe...Most newborn screening laboratories use CE-marked or FDA-approved test-kits, like in routine clinical chemistry. National regulations require only minimal evaluation from the customer, if the test-kits are used as specified by the manufacturer. The microtiter-based kit-concept is often based on the perception, that the laboratory always processes whole microtiter plates. However, in the daily routine, this is rather a rare exception, which leads to much higher costs per newborn, compared to the costs per assay in the test-kits. In addition the amount of wasted resources is quite high. Performance of the Neonatal Total Galactose kit from Perkin Elmer was tested. We have determined specificity, limit of detection (LOD), limit of quantitation (LOQ), intra and inter assay variation, recovery, stability of measuring signal and reagents. Results were also compared with the Astoria Pacific Spot Check System. In addition, we had (by chance) the opportunity to test 2 kits, which were already expired for more than 3 years. LOD was 165 - 306 μmol/L and LOQ 475 - 703 μmol/L, depending on the definition of LOD/LOQ. Mean recovery was 112.8%, intra assay CVs were 11.3, 7.3, 4.0, and 3.0, and inter assay CVs 28.7, 15.9, 7.8, and 9.3, at 220, 590, 1200, and 2060 μmol/L respectively. Reconstituted and mixed reagents must be used within some hours, and were unstable even if stored at -20℃. However, if the reconstituted galactose substrate reagent and galactose oxidase reagent were only mixed according to the daily requirements, and the rest stored separately at -20℃, they were stable for at least 12 days. The performance of the expired test-kits did not differ from the others. The performance of the Total Galactose kit is comparable to other tests used for newborn screening. However, we could significantly reduce the costs per newborn and reduce unnecessary production of waste, by thorough validation and modification of the assay procedures.展开更多
Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese exp...Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.展开更多
Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study....Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.” The authors present three metachromatic leukodystrophy(MLD) patients treated with gene therapy and claim stabilization or even improvement, despite advanced symptomatic disease stage. The metachromatic leukodystrophy initiative(MLDi)(Schoenmakers et al., 2022), an international collaborative network and registry for MLD, urges caution in interpreting these results, as the evidence raises several critical concerns. These claims risk fostering false hope among MLD patients and their families, particularly given the significant gaps in the data provided(Fig. 1).展开更多
Background:The aim of this pilot study in Beijing,China,was to validate a screening system for early detection of biliary atresia(BA)by using a modified version of the stool color card(SCC).Methods:From 2013 to 2014,a...Background:The aim of this pilot study in Beijing,China,was to validate a screening system for early detection of biliary atresia(BA)by using a modified version of the stool color card(SCC).Methods:From 2013 to 2014,a total of 29799 live born infants were screened.SCC was distributed in maternal facilities.Guardians were asked to check their infants’stool colors daily using SCC up until four months after birth.The screening results among 92.5%of participants were reported.Cases deemed as high risk were referred to a surgical department immediately.Results:Based on the results reported by the guardians,24 infants showed pale-pigmented stools,of which two males without obvious signs of jaundice were diagnosed with BA at 52 and 55 days of age,respectively.The sensitivity was 100%and specificity was 99.9%.Four infants were confirmed as having other diseases.Two female patients failed to be screened by the SCC because they had severe jaundice and were referred to the Neonatal Intensive Care Unit after birth.They were diagnosed as BA at 14 and 17 days after birth,respectively.The overall prevalence of BA in this study was 1.3 in 10000 live births.Conclusion:The modified SCC was effective and feasible for early detection of BA,especially for patients with no apparent jaundice.展开更多
Background Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifi able causes. We searched for an association between abnormal thyroid levels after birth and INHB. Meth...Background Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifi able causes. We searched for an association between abnormal thyroid levels after birth and INHB. Methods Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program. Results Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no signifi cant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had signifi cant asso-ciation with INHB: TT4 ≥ 13 μg/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong eff ect of mode of delivery on possible signifi cant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 μg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confi dence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association. Conclusions INHB was signifi cantly associated with birth on 38-38.6 week and TT4 (≥ 13 μg/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.展开更多
Introduction Methylmalonic acidemia(MMA)is a disorder of autosomal recessive inheritance,with an estimated prevalence of 1:50,000.First-tier clinical diagnostic tests often return many false positives[fve false positi...Introduction Methylmalonic acidemia(MMA)is a disorder of autosomal recessive inheritance,with an estimated prevalence of 1:50,000.First-tier clinical diagnostic tests often return many false positives[fve false positive(FP):one true positive(TP)].In this work,our goal was to refne a classifcation model that can minimize the number of false positives,currently an unmet need in the upstream diagnostics of MMA.Methods We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction.We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients,followed by additional ratio feature construction.Feature selection strategies(selection by flter,recursive feature elimination,and learned vector quantization)were used to determine the input set for evaluating the performance of 14 classifcation models to identify a candidate model set for an ensemble model development.Results Our work identifed computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity.The best results[area under the receiver operating characteristic curve(AUROC)of 97%,sensitivity of 92%,and specifcity of 95%]were obtained utilizing an ensemble of the algorithms random forest,C5.0,sparse linear discriminant analysis,and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor.The model achieved a good performance trade-of for a screening application with 6%false-positive rate(FPR)at 95%sensitivity,35%FPR at 99%sensitivity,and 39%FPR at 100%sensitivity.Conclusions The classifcation results and approach of this research can be utilized by clinicians globally,to improve the overall discovery of MMA in pediatric patients.The improved method,when adjusted to 100%precision,can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.展开更多
基金This project is supported by a grant from the National Natural Sciences Foundation (No. 30100207)a grant from the Top Ten Scientific Research Programs of Shandong Province (No. 2004GG3202003)
文摘To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening （UNHS） were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn＇t pass the heating screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit （NICU）, neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity （OR=16.285, 95% CI 3.379--78,481）, neonatal disease （OR=34;968, 95% CI 2.720 449.534）, family history of congenital hearing loss （OR=69.488, 95% CI 4.417--1093.300） and birth weight （OR=0.241, 95% CI 0.090--0.648）. It is concluded that parity, neonatal disease and family history of heating loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.
基金Supported by Shenzhen Key Medical Discipline Construction Fund,Grant/Award,No.SZXK031.
文摘BACKGROUND Acephalic spermatozoa syndrome(ASS)is an extremely rare form of severe teratozoospermia,where in most of the sperm either appear to lack heads or have disconnected or poorly connected heads and tails.CASE SUMMARY We reported the case of a male patient with secondary infertility whose sperm showed typical ASS upon morphological analysis.Whole-exome sequencing was performed on the patient’s peripheral blood,which revealed two heterozygous variants of the PMFBP1 gene:PMFBP1c.414+1G>T(p.?)and PMFBP1c.393del(p.C132Afs*3).CONCLUSION It is speculated that the compound homozygous mutation of PMFBP1 may be the cause of ASS.We conducted a literature review in order to provide the basis for genetic counseling and clinical diagnosis of patients with ASS.
文摘This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the 'March of Dimes Global Network for Maternal and Infant Health(GNMIH)' ,allows developing country experts to more easily share their knowledge,experience,skills and materials in ways that can improve women's,maternal,newborn and child health in lower-income countries. This report begins with a brief description of the March of Dimes and its Global Programs which oversees the GNMIH. It then discusses the structure of the GNMIH,with an emphasis on the benefits and challenges of working within the network,and concludes with a brief description of the acti-vities of network members.
文摘Most newborn screening laboratories use CE-marked or FDA-approved test-kits, like in routine clinical chemistry. National regulations require only minimal evaluation from the customer, if the test-kits are used as specified by the manufacturer. The microtiter-based kit-concept is often based on the perception, that the laboratory always processes whole microtiter plates. However, in the daily routine, this is rather a rare exception, which leads to much higher costs per newborn, compared to the costs per assay in the test-kits. In addition the amount of wasted resources is quite high. Performance of the Neonatal Total Galactose kit from Perkin Elmer was tested. We have determined specificity, limit of detection (LOD), limit of quantitation (LOQ), intra and inter assay variation, recovery, stability of measuring signal and reagents. Results were also compared with the Astoria Pacific Spot Check System. In addition, we had (by chance) the opportunity to test 2 kits, which were already expired for more than 3 years. LOD was 165 - 306 μmol/L and LOQ 475 - 703 μmol/L, depending on the definition of LOD/LOQ. Mean recovery was 112.8%, intra assay CVs were 11.3, 7.3, 4.0, and 3.0, and inter assay CVs 28.7, 15.9, 7.8, and 9.3, at 220, 590, 1200, and 2060 μmol/L respectively. Reconstituted and mixed reagents must be used within some hours, and were unstable even if stored at -20℃. However, if the reconstituted galactose substrate reagent and galactose oxidase reagent were only mixed according to the daily requirements, and the rest stored separately at -20℃, they were stable for at least 12 days. The performance of the expired test-kits did not differ from the others. The performance of the Total Galactose kit is comparable to other tests used for newborn screening. However, we could significantly reduce the costs per newborn and reduce unnecessary production of waste, by thorough validation and modification of the assay procedures.
文摘Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
文摘Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.” The authors present three metachromatic leukodystrophy(MLD) patients treated with gene therapy and claim stabilization or even improvement, despite advanced symptomatic disease stage. The metachromatic leukodystrophy initiative(MLDi)(Schoenmakers et al., 2022), an international collaborative network and registry for MLD, urges caution in interpreting these results, as the evidence raises several critical concerns. These claims risk fostering false hope among MLD patients and their families, particularly given the significant gaps in the data provided(Fig. 1).
基金supported by grants from both Beijing Natural Science Foundation of China(7133241)the National Center for Child Health and Development of Japan(25-5).
文摘Background:The aim of this pilot study in Beijing,China,was to validate a screening system for early detection of biliary atresia(BA)by using a modified version of the stool color card(SCC).Methods:From 2013 to 2014,a total of 29799 live born infants were screened.SCC was distributed in maternal facilities.Guardians were asked to check their infants’stool colors daily using SCC up until four months after birth.The screening results among 92.5%of participants were reported.Cases deemed as high risk were referred to a surgical department immediately.Results:Based on the results reported by the guardians,24 infants showed pale-pigmented stools,of which two males without obvious signs of jaundice were diagnosed with BA at 52 and 55 days of age,respectively.The sensitivity was 100%and specificity was 99.9%.Four infants were confirmed as having other diseases.Two female patients failed to be screened by the SCC because they had severe jaundice and were referred to the Neonatal Intensive Care Unit after birth.They were diagnosed as BA at 14 and 17 days after birth,respectively.The overall prevalence of BA in this study was 1.3 in 10000 live births.Conclusion:The modified SCC was effective and feasible for early detection of BA,especially for patients with no apparent jaundice.
文摘Background Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifi able causes. We searched for an association between abnormal thyroid levels after birth and INHB. Methods Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program. Results Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no signifi cant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had signifi cant asso-ciation with INHB: TT4 ≥ 13 μg/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong eff ect of mode of delivery on possible signifi cant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 μg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confi dence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association. Conclusions INHB was signifi cantly associated with birth on 38-38.6 week and TT4 (≥ 13 μg/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.
基金supported by the National Key R&D Program of China grand No.2022YFC2703103the Clinical Research Plan of SHDC(SHDC2020CR6028,SHDC2020CR1047B)+1 种基金the Science and Technology Commission of Shanghai Municipality grant 22Y11906900the Second Century Fund(C2F),Chulalongkorn University,Bangkok,Thailand.
文摘Introduction Methylmalonic acidemia(MMA)is a disorder of autosomal recessive inheritance,with an estimated prevalence of 1:50,000.First-tier clinical diagnostic tests often return many false positives[fve false positive(FP):one true positive(TP)].In this work,our goal was to refne a classifcation model that can minimize the number of false positives,currently an unmet need in the upstream diagnostics of MMA.Methods We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction.We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients,followed by additional ratio feature construction.Feature selection strategies(selection by flter,recursive feature elimination,and learned vector quantization)were used to determine the input set for evaluating the performance of 14 classifcation models to identify a candidate model set for an ensemble model development.Results Our work identifed computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity.The best results[area under the receiver operating characteristic curve(AUROC)of 97%,sensitivity of 92%,and specifcity of 95%]were obtained utilizing an ensemble of the algorithms random forest,C5.0,sparse linear discriminant analysis,and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor.The model achieved a good performance trade-of for a screening application with 6%false-positive rate(FPR)at 95%sensitivity,35%FPR at 99%sensitivity,and 39%FPR at 100%sensitivity.Conclusions The classifcation results and approach of this research can be utilized by clinicians globally,to improve the overall discovery of MMA in pediatric patients.The improved method,when adjusted to 100%precision,can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.
