title: 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.
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.
authors.affiliation: Genetic Metabolic Disorders Service, Children's Hospital at Westmead, Sydney, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Shanti
authors.forename: M
authors.initials: M
authors.lastname: Silink
authors.forename: K
authors.initials: K
authors.lastname: Bhattacharya
authors.forename: N J
authors.initials: NJ
authors.lastname: Howard
authors.forename: K
authors.initials: K
authors.lastname: Carpenter
authors.forename: M
authors.initials: M
authors.lastname: Fietz
authors.forename: P
authors.initials: P
authors.lastname: Clayton
authors.forename: J
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D044903:Congenital Hyperinsulinism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology; D009154:Mutation; D046768:Nesidioblastosis / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology; D009849:Olivopontocerebellar Atrophies / Q000209:etiology / Q000473:pathology; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency / Q000235:genetics
chemical_list: D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human