title: Intrauterine cardiomyopathy and cardiac mitochondrial proliferation in mitochondrial trifunctional protein (TFP) deficiency.
abstract: Because of a switch in energy-producing substrate utilization from glucose in the fetal period to fatty acids postnatally, intrauterine morbidity of fatty acid oxidation defects has widely been denied. We report the intrauterine development of severe cardiomyopathy in a child with mitochondrial trifunctional protein deficiency after 27 weeks of gestation. The child was born at 31 weeks of gestation and died on day 3 of life. Severe cardiac mitochondrial proliferation was observed. Molecular analysis of both TFP genes was performed and confirmed a homozygous mutation in the TFP alpha-subunit introducing a stop codon at amino acid position 256 (g.871C>T, p.R256X). Despite severe intrauterine decompensation in our patient, no HELLP-syndrome or acute fatty liver of pregnancy was observed in the mother. In the pathogenesis of maternal HELLP-syndrome, toxic effects of accumulating long-chain hydroxy-acyl-CoAs or long-chain hydroxy-acylcarnitines are suspected. In our patient, acylcarnitine analysis on day 2 of life during severest metabolic decompensation did not reveal massive accumulation of long-chain hydroxy-acylcarnitines in blood, suggesting other pathogenic factors than toxic effects. The most important pathogenic mechanism for the development of intrauterine cardiomyopathy appears to be significant cardiac energy deficiency. In conclusion, our report implicates that fatty acid oxidation does play a significant role during intrauterine development with special regard to the heart. Severe cardiac mitochondrial proliferation in TFP deficiency suggests pathophysiologically relevant energy deficiency in this condition.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Moorenstr. 5, 40225 Duesseldorf, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Moorenstr. 5, 40225 Duesseldorf, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Oldenburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Cloppenburg
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Oldenburg, Germany.
authors.forename: Reinald
authors.initials: R
authors.lastname: Motz
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Moorenstr. 5, 40225 Duesseldorf, Germany.
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.affiliation: Institute of Pathology, University Tuebingen, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bueltmann
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Oldenburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Korenke
mesh_terms: D009202:Cardiomyopathies / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D049109:Cell Proliferation; D018389:Codon, Nonsense; D003241:Consanguinity; D017809:Fatal Outcome; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics; D032342:Muscle Cells / Q000166:cytology / Q000201:enzymology / Q000473:pathology / Q000502:physiology*; D010084:Oxidation-Reduction; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D018389:Codon, Nonsense; D005227:Fatty Acids; D009097:Multienzyme Complexes; D063991:Mitochondrial Trifunctional Protein