Maturity onset Diabetes of the Young (MODY)

Introduction

Diabetes is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or insulin action or both. Several types of diabetes mellitus were described. Maturity onset diabetes of the young is a special type. The different MODY genotypes are associated with different clinical phenotypes. MODY should be considered in young people presenting with a typical family history (diabetes affecting a parent and 50% expression of the disease in the family) plus a form of early-onset diabetes which appears easy to control.

Maturity onset diabetes of the young (MODY) is a subtype of DM. It is characterized by autosomal dominant inheritance, early onset of hyperglycemia, and impairment in insulin secretion. Several monogenic forms of DM have been identified.

1. MODY 1

2. MODY 2

3. MODY 3

4. MODY 4

5. MODY 5

6. MODY 6

The glucokinase gene is intimately involved in the glucose-sensing mechanism within the pancreatic beta-cell. The hepatic nuclear factor (HNF) genes and the insulin promoter factor-1 (IPF-1) gene control nuclear transcription in the beta-cell where they regulate its development and function. Abnormal nuclear transcription genes may cause pancreatic agenesis or more subtle progressive pancreatic damage

MODY 1

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 4a.

Chromosomal location	20q
Proportion of all MODY cases	5%
Onset	Teens to thirties
Progression	Progressive hyperglycemia
Microvascular complications	Frequent
Other features	None

MODY 2

MODY 2 is the result of mutations in the glucokinase gene that lead to mild-to-moderate hyperglycemia. Glucokinase catalyzes the formation of glucose-6-phosphate from glucose.

Chromosomal location	7q
Proportion of all MODY cases	15%
Onset	Present from birth
Progression	Little deterioration with age
Microvascular complications	Rare
Other features	Reduced birthweight

MODY 3

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 1a.

Chromosomal location	12q
Proportion of all MODY cases	12q
Onset	teens/twenties
Progression	Progressive hyperglycemia
Microvascular complications	frequent
Other features	sensitive to sulphonylurea

MODY 4

This is a rare variant caused by mutations in the insulin promoter factor (IPF) 1, which is a transcription factor that regulates pancreatic development and insulin gene transcription.

Chromosomal location	13q
Proportion of all MODY cases	<1%
Onset	teens to thirties
Progression	Progression unclear
Microvascular complications	few data
Other features	Pancreatic agenesis in homozygotes

MODY 5

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 1b.

Chromosomal location	17q
Proportion of all MODY cases	2%
Onset	Teens/twenties
Progression	Progression unclear
Microvascular complications	Frequent
Other features	Renal cysts, Proteinuria, Renal failure

MODY 6

This is due to the mutation in the neurogenic differention factor1 (NeuroD1)

Chromosomal location	2q
Proportion of all MODY cases	<7%
Onset
Progression
Microvascular complications
Other features