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

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 investigated a novel c.59 C > T variant of the HSD17B10 gene and the clinical phenotypic features of HSD10 MD (neonatal form) patients. Results We describe a Chinese boy 2 months and 12 days old 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 hemizygous variant, c.59 C > T (p.S20L), of the HSD17B10 gene. Molecular dynamics simulation analysis and protein structural analysis suggested that the c.59 C > T (p.S20L) variant may disrupt the conformational stability of the protein. On the basis of the combined results of phenotypic analysis, molecular genetic analysis, protein structural analysis and molecular dynamics simulation analysis, this novel variant 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.59 C > T HSD17B10 variant suggested a neonatal form of the HSD10 mitochondrial disease phenotype in a patient 2 months and 12 days old, broadening the variant spectrum of HSD17B10-related disease.