medwireNews: Prematurity should not deter physicians from requesting genetic testing of hyperglycaemic infants, say researchers.
Andrew Hattersley (University of Exeter Medical School, UK) and colleagues found that, although it was a less common cause of hyperglycaemia in premature than term infants, monogenic diabetes was sufficiently frequent to warrant referral for genetic investigations.
The team identified a genetic cause in 83% of 604 investigated infants who were born at a gestational age of at least 37 weeks and in 66% of 146 infants born preterm. The lower rate among preterm infants was caused by a particularly low rate of just 31% among very premature infants, born at less than 32 weeks’ gestation.
But because these 13 patients accounted for less than 2% of those investigated, the researchers advise genetic referral of preterm infants only if they are born after 32 weeks’ gestation and do not have septicaemia.
“Testing before this gestational age should probably be limited to those patients in whom hyperglycemia persists until their corrected gestational age is 32 weeks”, they write in Pediatrics.
However, they stress that prematurity per se should not deter clinicians from requesting genetic analysis in hyperglycaemic infants, particularly as the infants with monogenic diabetes in their study had no distinguishing clinical features and diagnosis has the potential to “radically alter the optimum treatment”.
Mutations in KCNJ11 were significantly less common in preterm than term infants, at 21% versus 34%, and mutations in ABCC8 were as common, at 16% versus 18%. But together these potassium channel mutations accounted for 37% of the mutations among the preterm infants.
Determining this genetic diagnosis is particularly important, says the research team, as these patients “are likely to be successfully transferred from insulin onto oral sulphonylureas with an improvement in glycemic control.”
But they add: “Identifying neonatal diabetes due to other genetic causes is also recommended to provide prognostic information on disease progression, screening for comorbidities, and genetic counseling for affected future pregnancies.”
Methylation defects at chromosome 6q24 and mutations in GATA6 were both more common in preterm than term infants, at 27% versus 12% and 9% versus 2%, respectively. The latter, say Hattersley and colleagues, has not been previously reported “but is not unexpected”, given the mutation is associated with severe intrauterine growth retardation and cardiac abnormalities, which may trigger spontaneous or elective early delivery.
By Eleanor McDermid
Pediatrics 2016; Advance online publication
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