A novel c.59C>T variant of the HSD17B10 gene as a possible cause of HSD10 mitochondrial disease with hepatic dysfunction: a case report and review of the literature

Abstract

Background Pathogenic HSD17B10 gene variants cause HSD10 mitochondrial disease (HSD10 MD), which results in a wide spectrum of symptoms ranging from mild to severe. Typical symptoms include intellectual disability, choreoathetosis, cardiomyopathy, neurodegeneration, and abnormal behavior. This study aimed to investigate a novel c.59C > T variant of the HSD17B10 gene and the clinical phenotypic features of HSD10 MD (neonatal form) patients. Results We describe a 2-month and 12-day-old Chinese boy with intellectual disability, metabolic acidosis, hyperlactatemia, hypoglycemia, cholestatic hepatitis and myocardial enzyme levels, slightly elevated 2-methyl-3-hydroxybutyric acid (2M3HBA) levels and early death. Although full-length sequencing of the mitochondrial genome was normal, whole-exome sequencing of the proband and his parents revealed a novel de novo heterozygous variant, c.59C > T (p.S20L), of the HSD17B10 gene. Molecular dynamics simulation analysis and protein structural analysis have suggested that the c.59C > T (p.S20L) mutation may disrupt the conformational stability of the protein. According to the combined results of phenotypic analysis, molecular genetic analysis, protein structural analysis and molecular dynamics simulation analysis, this novel mutation is currently considered a likely pathogenic variant. HSD10 MD (neonatal form) can lead to hepatic dysfunction. Conclusions HSD10 MD (neonatal form) can lead to hepatic dysfunction. The de novo c.59C > T HSD17B10 variant suggested a neonatal form of the HSD10 mitochondrial disease phenotype in a 2-month and 12-day-old patient, broadening the variant spectrum of HSD17B10-related disease.