[Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency].

Objective: To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).

Methods: Two 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.

Results: Both 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 glutaconic 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 variant (PVS1+PM2_Supporting+PP4).

Conclusion: Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.