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A hungry baby fails to thrive

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Q1: What is the diagnosis?

The diagnosis is neonatal diabetes mellitus, which is defined as persistent hyperglycaemia in term infants, within the first six weeks of life, requiring insulin for two or more weeks. Alternative names are temporary idiopathic neonatal hyperglycaemia, neonatal pseudodiabetes mellitus, transient diabetes of early infancy, and congenital temporary diabetes mellitus.1

Q2: What is the likely long term outcome?

Neonatal diabetes differs from insulin dependent (type I) diabetes in that it has a highly variable course. About half of these infants have permanent diabetes, and half have a period of remission, although 65% of the transient forms subsequently become diabetic again.2 The transient and permanent forms can only be distinguished by their clinical course.1 Infants with the transient form usually become euglycaemic without insulin treatment within the first year.3

Q3: What is the genetic linkage to this condition?

Molecular DNA analysis testing of infants with transient neonatal diabetes has recently shown a paternal uniparental disomy of chromosome 6. This refers to the inheritance of both 6th chromosomes from one parent only, with no contribution from the other. The findings predict that transient neonatal diabetes is due to the overexpression of an imprinted gene at 6q22-23.4

Outcome

He was initially managed in the paediatric intensive care unit with sedation, mechanical ventilation, plasma volume expansion (human plasma protein fraction and saline), intravenous insulin infusions, and anticonvulsants to control seizure activity. He was discharged home after three weeks when he was feeding well and on a twice daily subcutaneous insulin regimen. At 15 months his developmental milestones were all normal, and he remained on insulin with no apparent hypoglycaemic episodes.

Discussion

Only 0.5% of paediatric patients with diabetes develop the disease during the first year of life.1 Neonatal diabetes mellitus is one of the rarest forms of diabetes, with a reported incidence of 1 in 450 000 live births.2 In Northern Ireland, one case presents approximately every 16 years.

Babies with neonatal diabetes are classically small for dates, term infants, as found in the case presented. They develop hyperglycaemia and marked metabolic acidosis with severe dehydration (as shown in this case with low pH, low bicarbonate, and compensatory low carbon dioxide, from hyperventilation). The event here may have been precipitated by an intercurrent viral infection, manifested by the high white cell count and platelets.

Seventy five per cent of cases first present with symptoms within 10 days of birth.1 The picture of a lively, alert but grossly dehydrated infant is classical, in contrast to the semicomatose state and glazed eye appearance of severely dehydrated infants. Polyuria is difficult to recognise in the newborn. Rapid rehydration, in the presence of hypernatraemia (sodium 154 mmol/l), can cause cerebral oedema and subsequent seizure activity, if serum sodium falls too quickly. Balancing the correct fluid replacement over the first hours of the acute period requires very close monitoring of blood electrolytes. With few exceptions, most infants require exogenous insulin. After initiation of insulin therapy, weight gain usually accelerates.

Learning points

  • Neonatal diabetes mellitus is rare (1 in 450 000 births).

  • The majority of babies eventually have permanent diabetes.

  • Genetic linkage has been shown to uniparental disomy of chromosome 6.

Various suggestions to explain the pathogenesis of this condition have been proposed, including reduced insulin production from pancreatic dysmaturity, insulin resistance,3 and insulinopenia from a poor response of the pancreatic beta cell to hyperglycaemia.1 The fact that most babies are low birth weight may be related to the failure of insulin secretion, as insulin is one of the main growth factors in utero.4 Heredity plays an important part as approximately 25% of neonatal cases have an affected sibling, with boys and girls being equally affected.1 It has been suggested that the two phenotypes of transient and permanent neonatal diabetes have different genetic backgrounds, as the paternal uniparental disomy of chromosome 6 on DNA analysis, found in some cases with the transient form, has not been shown in the permanent form of neonatal diabetes.5

The overall outcome for general health and normal intellectual development is usually good. Complications of vasculopathy in long term follow up reports are rare.1 2 The prognosis is worst in permanent diabetes, onset of diabetes after 1 month of age, and associations with other rarer associated syndromes (Wolcott-Rallinson syndrome and X linked hyperuricaemia).2

Final diagnosis

Neonatal diabetes mellitus.

References

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