Clinical features:
(1) The presence of a strong family history of diabetes, involving at least 3 generations and/or with evidence of autosomal dominant inheritance.
(2) The onset of hyperglycemia as a child, adolescent or young adult, with slow progression to clinical diabetes over many years.
(3) Many patients are not obese.
(4) Insulin resistance is uncommon (unless the patient also has obesity-related Type 2 diabetes).
(5) Patients show a delayed and subnormal insulin secretory response, with insulin insufficiency (page 590, Fajans).
(6) Patients show a low rate of ketosis.
The syndromes are caused by the presence of a mutation that impairs beta cell function in the pancreas. Several mutations have been identified but others still need to be described.
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MODY
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Mutation
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MODY1
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hepatocyte nuclear factor (HNF) 4-alpha
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MODY2
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glucosekinase gene
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MODY3
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hepatocyte nuclear factor (HNF) 1-alpha
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MODY4
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insulin promoter factor 1
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MODY5
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hepatocyte nuclear factor (HNF) 1-beta
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The level of hyperglycemia is usually mild and can be controlled by diet and/or use of hypoglycemic agents. Some patients may have severe insulin deficiency (? double dose) and require insulin therapy.
A young child may be misdiagnosed as having insulin-dependent diabetes (Type 1). Insulin therapy may be unnecessary in these patients and may be associated with excessive morbidity.
It is important to distinguish MODY from Type 2 diabetes that occurs in obese children with insulin resistance. An obese child from a family with a MODY mutation may have both forms of diabetes.
