Clinical features and treatment of maturity onset diabetes of the young (MODY)

Figures & data

Table 1 Classification of single gene mutations resulting in monogenic diabetes

Gene	Prevalence amongst those with MODY	Other clinical features
HNF1A	30%–50%*	Common mutation. Highly penetrant. Large (>5 mmol/L) rise in 2-hour glucose levels on 75 g–OGTT. Progressive β-cell failure. Sensitivity to sulphonylureas.
GCK	30%–50%*	Common mutation. Raised fasting glucose levels, with small (<3 mmol/L) rise in 2 hour glucose following 75 g–OGTT. Mild hyperglycemia; generally does not require treatment.
HNF4A	5%	Presents in similar manner to HNF1A mutations. Associated with higher birth weight and transient neonatal hypoglycemia. Progressive β-cell failure. Sensitivity to sulphonylureas.
HNF1B	5%	Characterized by renal disease. Urogenital tract abnormalities in females.
INS	<1%	Wide clinical spectrum. Most present with neonatal diabetes, but may also present in early childhood and adulthood.
IPF1	<1%	Average age of onset is 35 years.^Citation7 IPF1 regulates early pancreatic development. Pancreatic agenesis seen in homozygotes and compound heterozygotes.^Citation83,Citation84
NEUROD1	<1% (fewer than five families reported)	Very rare, adult onset (mid-20s). Reduced insulin production (developmental β-cell dysfunction). Individuals may be overweight or obese, similar to type 2 diabetes.
CEL	<1% (fewer than five families reported)	Very rare, adult onset (mean age 36 years). Exocrine pancreatic insufficiency (dysfunction of the mature acinar cell). Pathophysiology of endocrine dysfunction not clear.
PAX4	<1% (fewer than five families reported)	Only two families described.

Note:

* Dependent on the populations studied.

Abbreviations: HNF1A, hepatocyte nuclear factor 1 homeobox A; GCK, glucokinase; HNF4A, hepatocyte nuclear factor 4 homeobox A; HNF1B, hepatocyte nuclear factor 1 homeobox B; IPF1, insulin promoter factor 1; NEUROD1, neurogenic differentiation 1; CEL, carboxyl ester lipase; PAX4, paired box 4.

Stoffers DA Ferrer J Clarke WL Habener JF Early-onset type-II diabetes mellitus (MODY4) linked to IPF1 Nat Genet 1997 17 2 138 139 9326926

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Schwitzgebel VM Mamin A Brun T Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1 J Clin Endocrinol Metab 2003 88 9 4398 4406 12970316

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Thomas IH Saini NK Adhikari A Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation Pediatr Diabetes 2009 10 7 492 496 19496967

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