Mol Genet Metab Rep. 2026 Sep;48
101329
Jia Hui Megan Loh,
May Oo Khin,
John Bassett,
Amal Mighell,
Sarah Jowett,
Sulleman Moreea,
Alison Woodall,
Priscilla Sia,
Afifah Hussain,
Amy Hufton,
Karolina M Stepien.
Congenital Disorder of Glycosylation type Ib (MPI-CDG) is a rare autosomal recessive metabolic disorder caused by deficiency of mannose-6-phosphate isomerase, resulting in impaired N-glycosylation. Unlike other CDG subtypes, MPI-CDG is not associated with neurodevelopmental impairment and is effectively treated with oral D-mannose supplementation. However, evidence guiding management during pregnancy is scarce, and D-mannose is generally avoided due to limited safety data. We describe the long-term course and pregnancy outcomes of a woman diagnosed with MPI-CDG in infancy. She was treated with oral D-mannose throughout childhood with good clinical response but demonstrated intermittent non-compliance in adulthood, complicated by hepatic fibrosis, protein-losing enteropathy, osteoporosis, anaemia, and musculoskeletal manifestations. She had two pregnancies without D-mannose supplementation. The first pregnancy was complicated by microcytic anaemia, hypoalbuminemia, pregnancy-induced cholestasis, and emergency caesarean section. A male infant was delivered and later diagnosed with Hirschsprung disease, requiring surgical correction with good outcome. Postpartum assessment of the mother demonstrated progression of liver disease to cirrhosis (F4). The second pregnancy proceeded with fewer complications and resulted in emergency caesarean delivery of a healthy female infant with normal postnatal glucose control and growth. This case contributes to the limited literature on pregnancy in MPI-CDG and illustrates that successful pregnancies are possible despite advanced multisystem disease and cessation of D-mannose therapy. It highlights the importance of multidisciplinary care, close hepatic and nutritional monitoring, and the need for further studies to clarify the safety and role of D-mannose supplementation during pregnancy.
Keywords: CDG Ib; Congenital glycosylation defects; MPI-CDG; Outcomes; Pregnancy