BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its ...BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.展开更多
基金Supported by Beijing Holistic Integrative Medicine Association Clinical Research Funding Program,No.ZHKY-2024-2209.
文摘BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.
