Novel HMGCS2 pathogenic variants in a Chinese family with mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA synthase deficiency

Pediatric Investigation

Wei Li¹  Jun Liu¹  Jun Guo²  Chanjuan Hao²  Xuyun Hu³  Suyun Qian⁴  Ruolan Guo⁴  Pengfei Zhang⁵ 

[1] Genetics and Birth Defects Control Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China;MOE Key Laboratory of Major Diseases in Children;National Center for Children's Health Beijing 100045 China;Beijing Key Laboratory for Genetics of Birth Defects Beijing Pediatric Research Institute;Department of Pediatric Intensive Care Unit Beijing Children's Hospital Capital Medical University;

关键词: HMGCS2 mutation;    Hypoketotic hypoglycemia;    Mitochondrial HMG‐CoA synthase deficiency;    Pediatric intensive care unit;    Whole‐exome sequencing;   

DOI  :  10.1002/ped4.12130

来源: DOAJ

【 摘 要 】

Abstract Importance Mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) synthase deficiency is a rare and underdiagnosed disorder with fewer than 30 patients reported worldwide. The application of whole‐exome sequencing in patients could improve our understanding of this disorder. Objective To identify the genetic causes and evaluate the phenotype of mitochondrial HMG‐CoA synthase deficiency in a pediatric patient with uncommon features that included ketosis and elevated lactate and ammonia. Methods The proband was referred to the pediatric intensive care unit of Beijing Children's Hospital and selected for molecular testing with whole‐exome sequencing. Her parents and sibling also underwent sequencing for segregation information. Results We identified two novel mutations (c.1347_1351delAGCCT/p.Ala450Profs*7 and c.1201G>T/ p.Glu401*) in the HMG‐CoA synthase‐2 gene (HMGCS2, NM_005518.3) in the proband and her brother. Both variants were classified as pathogenic variants according to the American College of Medical Genetics and Genomics/ Association for Molecular Pathology guidelines. Metabolic acidosis in the proband was corrected with continuous renal replacement therapy and she left hospital after 21 days of treatment. Interpretation Our results extend the genotypic and phenotypic spectrum of HMGCS2 mutation in mitochondrial HMG‐CoA synthase deficiency patients and serve as a reminder for physicians to consider mitochondrial HMG‐CoA synthase deficiency in newborns and children with coma and hypoketotic hypoglycemia after fasting.

【 授权许可】

Unknown