Congenital disorder of glycosylation type Ia: heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency

J Inherit Metab Dis. 2009 Dec:32 Suppl 1:S241-51. doi: 10.1007/s10545-009-1180-2. Epub 2009 Apr 27.

Abstract

We describe three patients with congenital disorder of glycosylation (CDG) type Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to diazoxide therapy as a common feature. The first patient, an infant girl, presented with recurrent vomiting, failure to thrive, liver impairment, hypothyroidism and a pericardial effusion. The second patient, also female, had a milder disease with single organ involvement, presenting as isolated hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment. The third patient, a boy presented with multi-organ manifestations including congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia, coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All three patients had a type 1 serum transferrin isoform pattern, and were subsequently found to have low phosphomannomutase activity, confirming the diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as a differential diagnosis in patients with persistent hyperinsulinaemic hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia.

Publication types

  • Case Reports

MeSH terms

  • Brain / pathology
  • Child, Preschool
  • Congenital Disorders of Glycosylation / complications
  • Congenital Disorders of Glycosylation / diagnosis*
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Hyperinsulinism
  • Diagnosis, Differential
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Multiple Organ Failure / etiology
  • Mutation
  • Nesidioblastosis / diagnosis
  • Nesidioblastosis / enzymology
  • Nesidioblastosis / etiology
  • Olivopontocerebellar Atrophies / etiology
  • Olivopontocerebellar Atrophies / pathology
  • Phosphotransferases (Phosphomutases) / deficiency
  • Phosphotransferases (Phosphomutases) / genetics

Substances

  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase 2, human

Supplementary concepts

  • Congenital disorder of glycosylation type 1A