抄録
3-Hydroxyisobutyryl-coenzyme A (CoA) hydrolase deficiency (HIBCHD; MIM: #250620) is a rare autosomal recessive inborn error of metabolism caused by a defect in the HIBCH enzyme, resulting in a deficiency of the conversion of 3-hydroxy-isobutyryl-CoA to 3-hydroxy-isobutyric acid, a critical step in valine catabolism. This neurodegenerative disease of infancy is associated with hypotonia, developmental delay, cerebral atrophy and lesions in the basal ganglia on magnetic resonance imaging (MRI). In this study, we describe two unrelated patients with infantile-onset progressive neurodegenerative disease and mutations in HIBCH identified using whole exome sequencing (WES). In Case 1, WES revealed a novel homozygous variant in the HIBCH gene: c.808A>G (p.Ser270Gly). In Case 2, a novel compound heterozygous mutation in the HIBCH gene is described: c.808A>G (p.Ser270Gly) and c.173A>G (p. Asn58Ser). Parent analysis revealed that c.808A>G (p.Ser270Gly) was inherited from the father and c.173A>G (p. Asn58Ser) from the mother. These novel mutations were predicted as a disease-causing mutation. Plasma acylcarnitine analysis was normal in both patients. Physical examination showed similar features, such as axial hypotonia and spastic hypertonia in the legs. The first patient presented with difficult-to-treat seizures, while the second patient has not yet experienced documented seizures. In conclusion, our findings would widen the mutation spectrum of HIBCH deficiency and the phenotypic spectrum of the disease. The potential genotype–phenotype correlation would be profitable for the correct diagnosis, treatment and integral management of patients with HIBCH deficiency.
