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Updated: Aug 11, 2026

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Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria
D Chitayat1, K Meagher-Villemure, O A Mamer
1Division of Medical Genetics, Montreal Children's Hospital, Quebec, Canada.
Abstract:
Monozygotic male twins born to nonconsanguineous parents had dysmorphic facial features, microcephaly, migrational brain disorder, and congenital intracerebral calcification. They excreted excessive amounts of 3-hydroxyisobutyric acid, a metabolite of valine, and had evidence of impaired oxidative metabolism and metabolic acidosis. The level of 3-hydroxyisobutyrate in stored samples of midtrimester amniotic fluid was found to be high. The association of 3-hydroxyisobutyric aciduria with brain dysgenesis is a newly recognized mendelian disorder; its recurrence in a family at risk is potentially avoidable by prenatal diagnosis.
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