title: A fetus with mitochondrial trifunctional protein deficiency: Elevation of 3-OH-acylcarnitines in amniotic fluid functionally assured the genetic diagnosis.
abstract: Mitochondrial trifunctional protein (TFP) is a multienzyme complex that catalyzes the last three steps of the β-oxidation cycle of long-chain fatty acids. In the prenatal diagnosis of TFP deficiency, acylcarnitine (AC) analysis has been considered difficult because of limited excretion of long-chain ACs into the fetal urine and hence into the amniotic fluid. Here, we report our experience with prenatally diagnosing TFP deficiency using AC analysis of amniotic fluid. The index case was a boy born at 38 weeks gestation and weighing 2588 g. He suddenly became unconscious and hypoglycemic and died on day 6 of life. Postmortem blood AC analysis and gene sequencing revealed TFP deficiency. Therefore, the parents underwent prenatal diagnoses for their subsequent 2 pregnancies. Mutation analysis suggested that one (Case 1) was affected and the other (Case 2) was not. AC analysis also demonstrated identical results, with significantly elevated 3-hydroxy-AC levels in the amniotic fluid of the affected pregnancy compared with those of heterozygotes and normal controls (n = 2 for heterozygotes and n = 8 for normal controls). Our findings suggest that AC analysis can functionally confirm results even in families with unidentified mutations, without raising issues related to maternal cell contamination. During prenatal diagnosis, misdiagnosis has to be avoided, and combining AC analysis with gene sequencing may result in more accurate prenatal diagnosis of TFP deficiency.
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1, Kusunokicho, Chuo, Kobe, Hyogo 6500017, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Bo
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Ennya-cho, Izumo, Shimane 6938501, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
keywords: Acylcarnitine analysis; Fatty acid oxidation; HADHA OMIM: 600890, GDB: 434026, GenBank: NM_000182; HADHA gene; HADHB OMIM: 143450, GDB: 344953, GenBank: NM_000183; Mitochondrial trifunctional protein (TFP); Prenatal diagnosis