Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia

Patients with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency present with a Reye-like syndrome, cardiomyopathy, or sudden unexpected de ath. We describe an unusual presentation in a patient with unsuspected LCHA D deficiency. The proband presented at 2 months of age with an acute infant ile hypocalcaemia and vitamin D deficiency associated with occult, unexplai ned cholestatic liver disease. Sudden, unexpected death occurred at 8 month s. Molecular analysis revealed homozygosity for the prevalent LCHAD (1528G > C, E474Q) mutation. The mother had pre-eclampsia during the third trimest er of her pregnancy. In a subsequent pregnancy, she developed severe acute fatty liver of pregnancy (AFLP) and intrauterine fetal death at 33 weeks of gestation. In conclusion, infantile hypocalcaemia is an unusual phenotype associated with LCHAD deficiency. The maternal pregnancy history documents that fetal LCHAD deficiency is associated with a spectrum of maternal illne sses ranging from pre-eclampsia to life-threatening AFLP.