Diagnostic pitfall in antenatal manifestations ofCPT IIdeficiency

Abstract

Carnitine palmitoyltransferase II (CPT2) deficiency is a rare inborn error of mitochondrial fatty acid metabolism associated with various phenotypes. Whereas most patients present with postnatal signs of energetic failure affecting muscle and liver, a small subset of patients presents antenatal malformations including brain dysgenesis and neuronal migration defects. Here, we report recurrence of severe cerebral dysgenesis with Dandy-Walker malformation in three successive pregnancies and review previously reported antenatal cases. Interestingly, we also report that acylcarnitines profile, tested retrospectively on the amniotic fluid of last pregnancy, was not sensitive enough to allow reliable prenatal diagnosis of CPT2 deficiency. Finally, because fetuses affected by severe cerebral malformations are frequently aborted, CPT2 deficiency may be underestimated and fatty acid oxidation disorders should be considered when faced with a fetus with Dandy-Walker anomaly or another brain dysgenesis.

Antenatal manifestations of inborn errors of metabolism: biological diagnosis

“…2). Conversely, since long-chain acylcarnitines are not eliminated in urine but in bile, CPT2 deficiency cannot be reliably diagnosed by acylcarnitine analysis in AF (Boemer et al 2016). Although it has never been performed, it is most probable that acylcarnitine profiling in fetal plasma or blood is diagnostic.…”

“…Mutation analysis of the corresponding genes, ETFA, ETFB,a n d ETFDH for MADD, and CPT2 for CPT2 deficiency, are then necessary to confirm the diagnosis. Because fetuses affected by severe cerebral malformations are frequently aborted, Boemer et al (2016) suggest that fatty acid oxidation disorders may be underestimated and should be considered when faced with a fetus with Dandy-Walker or another brain dysgenesis, especially in cases with intrafamilial recurrence or…”

Implementation of a fast method for the measurement of carnitine palmitoyltransferase 2 activity in lymphocytes by tandem mass spectrometry as confirmation for newborn screening

“…S.B., M.S., and U.S. declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was not necessary as the examinations were carried out as part of routine diagnostics.…”

“…The rarest phenotype is the neonatal form (OMIM 608836), which is often lethal. In addition to the symptoms of the infantile phenotype, this form is associated with facial abnormalities and structural malformations such as cystic renal dysplasia, brain dysgenesis, and liver calcifications …”

“…In addition to the symptoms of the infantile phenotype, this form is associated with facial abnormalities and structural malformations such as cystic renal dysplasia, brain dysgenesis, and liver calcifications. [5][6][7][8] With the introduction of tandem mass spectrometry in newborn screening (NBS) programs, it has become possible to identify fatty acid oxidation disorders after birth by analyzing acylcarnitines in dried blood spots. In case of CPT2 deficiency, the most specific parameter is the ratio (C16 + C18:1)/C2.…”