Organic Aciduria Disorders in Pregnancy: An Overview of Metabolic Considerations

Abstract

Organic acidurias are a heterogeneous group of rare inherited metabolic disorders (IMDs) caused by a deficiency of an enzyme or a transport protein involved in the intermediary metabolic pathways. These enzymatic defects lead to an accumulation of organic acids in different tissues and their subsequent excretion in urine. Organic acidurias include maple syrup urine disease, propionic aciduria, methylmalonic aciduria, isovaleric aciduria, and glutaric aciduria type 1. Clinical features vary between different organic acid disorders and may present with severe complications. An increasing number of women with rare IMDs are reporting successful pregnancy outcomes. Normal pregnancy causes profound anatomical, biochemical and physiological changes. Significant changes in metabolism and nutritional requirements take place during different stages of pregnancy in IMDs. Foetal demands increase with the progression of pregnancy, representing a challenging biological stressor in patients with organic acidurias as well as catabolic states post-delivery. In this work, we present an overview of metabolic considerations for pregnancy in patients with organic acidurias.

Keywords: inborn errors of metabolism; organic aciduria; postpartum; pregnancy.

Figure 1

Main catabolic pathways of amino acids involved in organic aciduria. Abbreviations: GCDH: Glutaryl-CoA dehydrogenase, BCKDC: Branched-chain α-keto acid dehydrogenase complex, IVD: Isovaleryl-CoA dehydrogenase, PCC: Propionyl-CoA carboxylase, MCM: Methylmalonyl-CoA mutase, β-MC CoA: β-methylcrotonyl CoA, MGC CoA: β-methylglutaconyl CoA, HMG CoA: β-hydroxy-β-methylglutaryl CoA, MHB CoA: α-methylβ-hydroxyisobutyryl CoA, MAA CoA: α-methylacetoacetyl CoA, HIB CoA: β-hydroxyisobutyryl CoA, MMSA: methylmalonate semialdehyde, TCA: tricarboxylic acid, MSUD: Maple syrup urine disease, PA: Propionic aciduria, MMA: Methylmalonic aciduria, IVA: Isovaleric aciduria (IVA), GA1: Glutaric aciduria type 1, KIC: 2-keto-isocaproate/4-methyl-2-oxopentanoic acid, KMV: α-keto-β-methylvaleric acid/3-methyl-2-oxopentanoate, KIV: 2-keto-isovalerate/3-methyl-2-oxobutanoic acid, BCAT: branched-chain aminotransferase.