Abstract
Patients with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency present with a Reye-like syndrome, cardiomyopathy, or sudden unexpected death. We describe an unusual presentation in a patient with unsuspected LCHAD deficiency. The proband presented at 2 months of age with an acute infantile hypocalcaemia and vitamin D deficiency associated with occult, unexplained cholestatic liver disease. Sudden, unexpected death occurred at 8 months. Molecular analysis revealed homozygosity for the prevalent LCHAD (1528G>C, E474Q) mutation. The mother had pre-eclampsia during the third trimester 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 illnesses ranging from pre-eclampsia to life-threatening AFLP.
Similar content being viewed by others
References
Brackett JC, Sims HF, Rinaldo P, et al (1995) Two a–subunit donor splice site mutations cause human trifunctional protein deficiency. J Clin Invest 95: 2076–2082.
Dionisi–Vici C, Garavaglia B, Burlina AB, et al (1996) Hypoparathyroidism in trifunctional protein deficiency. J Pediatr 129: 159–162.
Hagenfeldt N, Venizelos N, Dobeln U (1995) Clinical and biochemical presentation of longchain 3–hydroxyacyl–CoA dehydrogenase deficiency. J Inher Metab Dis 18: 245–248.
Ibdah JA, Tein I, Dionisi–Vici C, et al (1998) Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype–phenotype correlation. J Clin Invest 102: 1193–1199.
IJlst L, Ushikubo S, Kamijo T, et al (1995) Long–chain 3–hydroxyacyl–CoA dehydrogenase deficiency: high frequency of the G1528C mutation with no apparent correlation with the clinical phenotype. J Inher Metab Dis 18: 241–244.
IJlst L, Ruiter JPN, Hoovers JMN. Jakobs ME, Wanders JA (1996) Common missense mutation G1528C in long–chain 3–hydroxyacyl–CoA dehydrogenase deficiency. J Clin Invest 98: 1028–1033.
Jackson S, Kler RS, Bartlett K, et al (1992) Combined enzyme defect of mitochondrial fatty acid oxidation. J Clin Invest 90: 1219–1225.
Pollitt RJ (1995) Disorders of mitochondrial long–chain fatty acid oxidation. J Inher Metab Dis 18: 473–490.
Sims HF, Brackett JC, Powell CK, et al (1995) The molecular basis of pediatric long chain 3–hydroxyacyl–CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. Proc Natl Acad Sci USA 92: 841–845.
Tyni T, Palotie A, Viinikka L, et al (1997a) Long–chain 3–hydroxyacyl–coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation in 13 patients. J Pediatr 130: 67–76.
Tyni T, Rapola J, Palotie A, Pihko H (1997b) Hypoparathyroidism in a patient with long chain 3–hydroxyacyl–CoA dehydrogenase deficiency caused by the G1528C mutation. J Pediatr 131: 766–768.
Tyni T, Ekholm E, Pihko H (1998) Pregnancy complications are frequent in long–chain 3– hydroxyacyl–CoA dehydrogenase deficiency. Am J Obstet Gynecol 178: 603–608.
Wilcken B, Leung K–C, Hammond J, Kamath R, Leonard JV (1993) Pregnancy and fetal LCHAD–deficiency. Lancet 341: 407–408.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ibdah, J.A., Dasouki, M.J. & Strauss, A.W. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia. J Inherit Metab Dis 22, 811–814 (1999). https://doi.org/10.1023/A:1005506024055
Issue Date:
DOI: https://doi.org/10.1023/A:1005506024055