Clinical Genetics
Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
Wu Xue, Fu Dongxia, Wang Huizhen, Wu Shengnan, Li Dongxiao, Chen Yongxing
Published 2024-02-10
Cite as Chin J Med Genet, 2024, 41(2): 199-204. DOI: 10.3760/cma.j.cn511374-20221010-00677
Abstract
ObjectiveTo explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).
MethodsTwo children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively.
ResultsBoth children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of the HMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of the HMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4).
ConclusionAcute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.
Key words:
3-hydroxy-3-Methylglutaryl-CoA lyase deficiency; Hypoglycemia; Metabolic acidosis; HMGCL gene
Contributor Information
Wu Xue
Department of Endocrinology and Inborn Error of Metabolism, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
Fu Dongxia
Department of Endocrinology and Inborn Error of Metabolism, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
Wang Huizhen
Department of Endocrinology and Inborn Error of Metabolism, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
Wu Shengnan
Department of Endocrinology and Inborn Error of Metabolism, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
Li Dongxiao
Henan Provincial Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory for Children′s Genetic and Metabolic Diseases, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
Chen Yongxing
Department of Endocrinology and Inborn Error of Metabolism, Children′s Hospital Affiliated to Zhengzhou University, Henan Children′s Hospital, Zhengzhou Children′s Hospital, Zhengzhou, Henan 450053, China
