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.
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.
Shanti
B
B
Genetic Metabolic Disorders Service, Children's Hospital at Westmead, Sydney, Australia.
Silink
M
M
Bhattacharya
K
K
Howard
N J
NJ
Carpenter
K
K
Fietz
M
M
Clayton
P
P
Christodoulou
J
J
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
D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human