3-hydroxyisobutyric aciduria

3-Hydroxyisobutyric aciduria (also known as 3-HIBA aciduria or beta-hydroxyisobutyric aciduria) is an extremely rare inborn error of valine metabolism. The condition results from a deficiency in the enzyme 3-hydroxyisobutyrate dehydrogenase (encoded by the HIBADH gene), which is involved in the catabolic pathway of the branched-chain amino acid valine. When this enzyme is deficient, 3-hydroxyisobutyric acid accumulates in the body and is excreted in elevated amounts in the urine. The disorder primarily affects the central nervous system and can also involve multiple organ systems. Key clinical features reported in affected individuals include developmental delay, intellectual disability, facial dysmorphism, and brain abnormalities. Some patients have presented with episodes of ketoacidosis, lactic acidosis, and failure to thrive. Congenital malformations, including cardiac defects and vertebral anomalies, have been described in some cases. The clinical presentation is variable, ranging from mild to severe, and some individuals may present in infancy with acute metabolic crises triggered by illness or catabolic stress. There is no specific curative treatment for 3-hydroxyisobutyric aciduria. Management is primarily supportive and symptomatic, focusing on dietary protein restriction (particularly valine intake), prevention of catabolic states, and prompt treatment of metabolic decompensation episodes. Carnitine supplementation may be considered in some cases. Long-term developmental support and multidisciplinary follow-up are important components of care. Only a small number of cases have been reported in the medical literature, making it difficult to fully characterize the natural history and prognosis of this condition.

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