3-Hydroxy-isobutyryl-CoA hydrolase deficiency. HIBCH deficiency. Leigh-like disease.
Incidence
Few HIBCH deficiency patients have been reported. The incidence ranges from the lowest population incidence in Europeans at 1 in 551,545 to highest incidence of 1 in 127,939 South Asian individuals (Stiles et al; 2015). Prevalence <1 / 1 000 000. Only 11 cases reported from the world literature including 2 of our patients. Update 2017/ MGJM.
Clinical Characteristics
HIBCH deficiency is a rare inborn error of metabolism caused by a defect in the HIBCH enzyme resulting in deficiency in the conversion of 3-hydroxy-isobutryl-CoA to 3-hydroxy-isobutyric acid, a critical step in valine catabolism. The syndrome is caused by mutations affecting the two alleles of the HIBCH gene, encoding 3-hydroxyisobutyryl-CoA hydrolase. The mode of transmission is autosomal recessive. The clinical characteristics are: hypotonia, poor feeding, motor delay, strabismus, by developmental delay of motor milestones in early infancy and neurological regression within the first year of life, visual inattention prompted an ophthalmological examination which may reveal optic atrophy. Some cases report recurrent vomiting, and seizures. When having seizures (most cases approximately 60%) show spasms, tonic generalized, absences, myoclonic. MRI abnormalities are striking for bilateral involvement of the basal ganglia increasing signal abnormalities of the basal ganglia (globus pallidus), reminiscent of Leigh syndrome, with varying degrees of white matter atrophy. Fibroblast activity of HIBCH was below normal level.
Precipitants
Intercurrent infections and febrile illnesses
Provocation Tests
None
Diagnostic Procedures
Skin biopsy for fibroblast culture (F): Fibroblast enzyme activity of HIBCH is below expected level.
Abnormal MRI with lesions in the globus pallidus and head of the caudate nucleus, basal ganglia atrophy, and persistent generalized brain atrophy and white matter changes
Genetic test: HIBCH gene abnormal mutation done by WES (whole exome sequencing), Cytogenetic location c.365A> G (p.Y122C), VUS c.632G> T (G211V), c.950G>A (p.G317E), c.219-220insTTGAATAG; (p.K73fsX86).