Impact of pregnancy on inborn errors of metabolism

Abstract

Once based mainly in paediatrics, inborn errors of metabolism (IEM), or inherited metabolic disorders (IMD) represent a growing adult medicine specialty. Individually rare these conditions have currently, a collective estimated prevalence of >1:800. Diagnosis has improved through expanded newborn screening programs, identification of potentially affected family members and greater awareness of symptomatic presentations in adolescence and in adulthood. Better survival and reduced mortality from previously lethal and debilitating conditions means greater numbers transition to adulthood. Pregnancy, once contraindicated for many, may represent a challenging but successful outcome. Successful pregnancies are now reported in a wide range of IEM. Significant challenges remain, given the biological stresses of pregnancy, parturition and the puerperium. Known diagnoses allow preventive and pre-emptive management. Unrecognized metabolic disorders especially, remain a preventable cause of maternal and neonatal mortality and morbidity. Increased awareness of these conditions amongst all clinicians is essential to expedite diagnosis and manage appropriately. This review aims to describe normal adaptations to pregnancy and discuss how various types of IEM may be affected. Relevant translational research and clinical experience will be reviewed with practical management aspects cited. Based on current literature, the impact of maternal IEM on mother and/or foetus, as well as how foetal IEM may affect the mother, will be considered. Insights gained from these rare disorders to more common conditions will be explored. Gaps in the literature, unanswered questions and steps to enhance further knowledge and systematically capture experience, such as establishment of an IEM-pregnancy registry, will be summarized.

Clouds over IMD? Perspectives for inherited metabolic diseases in adults from a retrospective cohort study in two Swiss adult metabolic clinics

“…In spite of the limitations discussed above, this retrospective study may give some indications on the outcome of these patients and indicate where the health system might be improved further: [1] adults with IMD are clearly an emerging population in Switzerland and may soon outnumber the pediatric population. Both children and adults with IMD require specific management and expertise from the health care providers, but the requirements are different and the setting is different (pediatric clinics vs. adult clinics), [2] as more than half of our patients developed organ-specific complications, a multidisciplinary team and disease-specific personalized health plans are necessary to monitor target organs and [3] as no patient is protected from metabolic decompensations, IMD clinics must be connected to tertiary hospitals offering intensive care units as well as availability of specific drugs. Hence the need for coordination of the management of these rare diseases at the national, and ideally international, level.…”

Comparison of phenylalanine tolerance in singleton and twin pregnancies in patients with phenylketonuria

“…8 Pregnancy in women with PKU can be viewed as a successful outcome of survival and transition into adulthood, achieving as normal a life as possible. 9 Physiologically, in the first two trimesters of pregnancy, maternal anabolism predominates, while from approximately 30 weeks' gestation, maternal catabolism with an accelerated breakdown of fat deposits is favored because of placental hormones and adipocytokines. 9,10 Anabolism is associated with increased Phe requirements.…”

Hyperornithinemia‐hyperammonemia‐homocitrullinuria syndrome in pregnancy: Considerations for management and review of the literature

“…Frequent laboratory monitoring of ammonia and plasma amino acids is recommended to adjust the amount of protein to maintain amino acids in the normal range. 9,10 Across all management plans, patients were prescribed varying dietary protein restriction, although it is difficult to quantify exactly recommended grams of protein per kilogram per patient. It varied from 40 to 25 g of dietary protein per day (our patient 5 ).…”

“…Most protocols for management of urea cycle disorders were general, and there was nothing in the literature regarding management during delivery. Therefore, we developed a management strategy in consultation of a multidisciplinary team including metabolic geneticists, maternalfetal-medicine specialists, anesthetists, internal medicine, metabolic dietician, and social worker (Table 1), which is supported by Wilcox et al 10 Caesarian section was thought to offer the best option for optimal metabolic control before, during, and after delivery. This is congruent with the recommendation by Häberle et al, 3 which states the patient should be well and surgery planned.…”