Abstract
We report five families with trifunctional protein deficiency in which, during pregnancy, three mothers experienced significant hepatic disease when carrying an affected fetus. Diagnoses were based on increased levels of long-chain hydroxyacylcarnitines and deficiencies of 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and 3-ketoacyl-CoA thiolase activity in fibroblasts. All affected infants lacked the common E474Q mutation associated with isolated LCHAD deficiency. This mutation is thought to be a predisposing factor for maternal hepatic disease in pregnancy. Our findings suggest that other defects in this enzyme complex might be responsible for maternal hepatic complications in pregnancy.
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REFERENCES
Ibdah J, Bennett MJ, Rinaldo P, et al (1999) A fetal fatty acid oxidation disorder as a cause of liver disease in pregnant women. N Engl J Med 340: 1723–1731.
IJlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ (1996) Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterisation and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localisation of the mitochondrial trifunctional protein alpha subunit. J Clin Invest 98: 1028–1033.
Innes AM, Seargeant LE, Balachandra K, et al (2000) Hepatic carnitine palmitoyl transferase I deficiency presenting as maternal illness in pregnancy. Pediatr Res 2000 47: 43–45.
Isaacs JD, Sims HF, Powell CK, et al (1996) Maternal acute fatty liver of pregnancy associ-ated with fetal trifunctional protein deficiency: molecular characterisation of a novel maternal mutant allele. Pediatr Res 40: 393–398.
Manning, Olpin SE, Pollitt RJ, Webley (1990) A comparison of [9,10–3H]palmitic and [9,10–3H]myristic acids for the defects of fatty acid oxidation in intact cultured fibroblasts. J Inherit Metab Dis 13: 58–68.
Mansouri A, Fromenty B, Durand F. Degott C, Bernuau J, Pessayre D (1996) Assessment of the prevalence of genetic metabolic defects in acute fatty liver of pregnancy. J Hepatol 25: 781–782.
Matern D, Strauss AW, Hillman SL, et al (1999) Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from newborn screening card by tandem mass spectro-metry and DNA analysis. Pediatr Res 46: 45–49.
Olpin SE, Manning NJ, Pollitt RJ, Clarke S (1997) Improved detection of long-chain fatty acid oxidation defects in intact cells using [9,10–3H]oleic acid. J Inherit Metab Dis 20: 415–419.
Reyes H, Sandoval L, Wainstein A, et al (1994) Acute fatty liver of pregnancy: a clinical study of 12 episodes in 11 patients. Gut 35: 101–106.
Schoeman MN, Batey RG, Wilcken B (1991) Recurrent acute fatty liver of pregnancy associ-ated with a fatty-acid oxidation defect in the offspring. Gastroenterology 100: 544–548.
Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA (1993) Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes and low platelets (HELLP syndrome). Am J Obstet Gynecol 169: 1000–1006.
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 Natal Acad Sci USA 92: 841–845.
Strauss AW, Bennett MJ, Rinaldo P, et al (1999) Inherited long chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal maternal interaction cause maternal liver disease and other pregnancy complications. Semin Perinatol 23: 100–112.
Treem WR, Rinaldo P, Hale DE, et al (1994) Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Hepatology 19: 339–345.
Treem WR, Shoup ME, Hale DE, et al (1996) Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Am J Gastroenterol 91: 2293–2300.
Tyni T, Pihko H (1999) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Acta Pediatr 88: 237–245.
Tyni T, Ekholm E, Pihko H (1998) Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Am J Obstet Gynecol 178: 603–608.
Wanders RJA, IJlst L, van Gennip AH, et al (1990) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid b-oxidation. J Inherit Metab Dis 13: 311–314.
Wanders RJA, Vreken P, Den Boer MEJ, Wijburg FA, van Gennip AH, IJlst L (1999) Dis-orders of mitochondrial fatty acyl-CoA b-oxidation. J Inherit Metab Dis 22: 442–487.
Wilcken B, Leung KC, Hammond J, Kamath R. Leonard JV (1993) Pregnancy and fetal long-chain 3-hydroxyacyl coenzyme A deficiency. Lancet 341: 407–408.
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Chakrapani, A., Olpin, S., Cleary, M. et al. Trifunctional protein deficiency: Three families with significant maternal hepatic dysfunction in pregnancy not associated with E474Q mutation. J Inherit Metab Dis 23, 826–834 (2000). https://doi.org/10.1023/A:1026712719416
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DOI: https://doi.org/10.1023/A:1026712719416