Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review

IntroductionWomen with inherited metabolic disorders, including those with previously life‐limiting conditions such as MMA, are reaching child‐bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored.MethodsPregnancies affected by maternal MMA were ascertained through study 04‐HG‐0127 “Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders” (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed.ResultsSeventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut‐ (one cobalamin responsive, three non‐responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5 % (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8 % (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57 % (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed.ConclusionAlthough there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147009/1/jimd0839.pd

Diagnosis of LCHAD/TFP deficiency in an at risk newborn using umbilical cord blood acylcarnitine analysis

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates. We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine analysis. Treatment was started immediately. Acylcarnitine analysis demonstrated findings that are consistent with a biochemical diagnosis of LCHAD/TFP deficiency. Patients with LCHAD/TFP deficiency should have treatment initiated as early as possible to avoid acute decompensation and minimize the long-term complications of the disorder including cardiomyopathy. In pregnancies at risk of having a child with LCHAD/TFP deficiency, umbilical cord blood sample is an efficient method to diagnose an inborn error of metabolism such as LCHAD/TFP deficiency