Clinical and biochemical improvement of very long-chain acyl-CoA dehydrogenase deficiency in pregnancy

Abstract

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an enzymatic defect of the fatty acid (FA) beta oxidation pathway. In catabolic states, such as labor and early postpartum period, patients are potentially prone to metabolic decompensation and subsequent rhabdomyolysis with increased risk for myoglobinuria and renal insufficiency. We report a 21-year-old primigravida with a previously characterized VLCAD deficiency, who experienced frequent and unprovoked episodes of rhabdomyolysis before pregnancy. As there was no published experience to guide her management, a detailed multidisciplinary care plan was established to minimize the potential morbidity. Although there is little known about the antenatal course of gravidae affected by VLCAD, we predicted that placental and fetal b-oxidation in an unaffected pregnancy may temporize or even improve maternal FA b-oxidation. Consistent with our prediction, we observed a significant clinical and biochemical improvement throughout her pregnancy, and she delivered vaginally with an uncomplicated postpartum course. We conclude that although VLCAD deficiency can present a therapeutic challenge during pregnancy, the beneficial placento-maternal metabolic interactions and the implementation of a proper peripartum management reassure a successful antenatal and perinatal outcome.

Adult‐onset very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD)

“…The median (range) age of patients at first visit was 31 (27-38) years, and the median (range) age of VLCADD onset was 26.5 (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) years. Two of the patients were men (patients 1, 2), and parental consanguinity was present for four patients (patients 1-4).…”

Successful management of pregnancy with very‐long‐chain acyl‐coenzyme A dehydrogenase deficiency

“…Previously, three of five patients with VCLADD were reported to experience myoglobinuria after their first delivery. 7 Cardiac failure during the postpartum period has also been reported. 9 In our case, myalgia started around the same time that she stopped breastfeeding and/or started menses.…”

“…Caution is also warranted after delivery and during puerperium. Previously, three of five patients with VCLADD were reported to experience myoglobinuria after their first delivery . Cardiac failure during the postpartum period has also been reported .…”

“…Mendez-Figueroa et al described a case of VLCADD in which the patient showed clinical and biochemical improvement during pregnancy. 7 They speculated that VLCAD activity within the placenta metabolized the maternal FA and resulted in a transient decrease in C14:1, with a return to abnormal levels after delivery. In fact, VLCAD has been found to be highly expressed in the human placenta from early gestation.…”

Effects of labor on placental fatty acid β oxidation

“…The present study and that of Oey et al [7] indicate that VLCAD is highly expressed in placenta making the first step of mitochondrial β-oxidation (ACAD step) unlikely to be a rate-limiting step. It could also explain why patients with this enzymatic defect tend to improve clinically during pregnancy [24]. The remaining three enzymatic reactions involved in chain-shortening long-chain FA are catalyzed by the octameric trifunctional protein (TFP).…”