Maternal Inborn Errors of Metabolism in Pregnancy: A Pregnancy Registry Protocol

Women with inherited metabolic disorders are reaching child bearing age more often due to
advances in early diagnosis and improved pediatric care. For many of these disorders, there
is very little information in the literature to guide the counseling and treatment of these
patients and their pregnancies.

The most information for the effects of an underlying inborn error of metabolism in pregnancy
derives from the study of phenylketonuria (PKU). From the knowledge gained through the
collection of information from multiple cases of pregnancy affected by PKU, important
management issues were identified. For example, children born to mothers with an unrestricted
diet were substantially more likely to have intellectual disability, microcephaly, and low
birth weights than women who maintained a phenylalanine restricted diet. The excess
phenylalanine poses long-term health risks to the developing fetus and now a vigilant
metabolic approach is recognized as mandatory in women with PKU desiring pregnancy.

Compared to PKU, most or all other intermediary metabolic disorders have been understudied.
For example, there are nine published cases of methylmalonic academia (MMA) in pregnancy and
one case of cobalamin C deficiency in pregnancy, and review articles have reported the same
cases. For other inborn errors of metabolism there is even less published or known. The
paucity of publication of pregnancy in IEMs other than PKU may be due to the lack of
organized research to address pregnancy management in metabolic disorders.

The objective of this study is to establish a pregnancy registry of women with inborn errors
of metabolism other than PKU. We will collect management plans, baseline laboratory values,
prenatal and postpartum course including metabolic and obstetrical issues, and fetal/neonatal
outcomes. This study will also investigate reproductive issues including infertility and use
of artificial reproductive technologies. A registry of this type will allow physicians and
patients to report varying management and outcomes, both positive and negative, with the
broader goal of delineating optimal maternal and fetal outcomes for these unique patient
populations. Our registry data would also serve as a vehicle to disseminate management
experience for all providers, recognizing that individual centers may not have sufficient
experience to make accurate management decisions on their own.

- INCLUSION CRITERIA:

- Patients clinically diagnosed with methylmalonic acidemia or another inborn error of
metabolism are eligible to participate; mutational and enzymatic status is preferred
but not required. Biochemical testing is required.

- Women with inborn errors of metabolism who have had a clinically documented prior
pregnancy, currently are pregnant or planning a pregnancy.

EXCLUSION CRITERIA:

- Patients with phenylketonuria or hyperphenylalaninemia.

- Anyone unwilling to provide informed consent (for themselves as adults, or on behalf
of their children as minors) or assent.

- Medical condition(s) or mental retardation are not in themselves reason for exclusion
if in the judgment of the referring physician this would involve no more than minimal
risk. We will make every effort to explain the study for the purpose of assent in a
manner that the family feels is both age and developmentally appropriate for that
individual.

- We will review a clinical description from the referring physician about a potential
research subject to determine that the subject is appropriate to enter into the study.
We reserve the right to exclude cases that are not definitively diagnosed by
metabolites and/or molecular genetics or related to our direct research interests. We
expect this to be a rare minority.