Background: 3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is a rare inborn error of valine catabolism associated with progressive neurological impairment. This retrospective cohort study aimed to characterize the clinical, biochemical, genetic, and respiratory chain profiles of HIBCH deficiency patients in Bahrain.
Methods: Eight HIBCH deficiency patients were evaluated from a larger cohort of 90 individuals assessed for Leigh-like syndrome at the metabolic clinic of Salmaniya Medical Complex, Bahrain, between 2000-2020. Clinical features, neuroimaging findings, biochemical profiles, genetic analyses, and respiratory chain activities were systematically examined.
Results: Developmental delay and acute encephalopathy were the main presenting symptoms. Neuroimaging demonstrated heterogeneous, often progressive basal ganglia and white matter changes. Biochemical profiling revealed elevated C4-OH acylcarnitine, with variable abnormalities in blood lactate, amino acids, and respiratory chain complexes. Genetic analysis identified a novel homozygous HIBCH variant (c.860A>G, p.Asp287Gly) in all patients. Despite clinical interventions, 5 of 8 patients exhibited severe, persistent developmental delay, and 3 patients succumbed to sepsis.
Conclusion: This study provides comprehensive characterization of the clinical, biochemical, and genetic changes in HIBCH deficiency patients in Bahrain, including the identification of a novel genetic variant. The progressive, debilitating nature of this disorder underscores the critical importance of early diagnosis and tailored management strategies for this rare metabolic condition.
Key words: HIBCH Deficiency, Leigh/Leigh-Like Syndrome, C4-OH, Valine Metabolism, Children.
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