Mody 5 E11.-

MODY is the acronym for "Maturity-onset Diabetes of the Young" and describes a group of autosomal-dominantly inherited, genetically heterogeneous, not always insulin-dependent forms of diabetes. The MODY forms of diabetes are caused by various disorders of beta cell function in the pancreas. The body weight of MODY patients is usually normal. Neither are any of the autoimmune phenomena characteristic of type 1 diabetes observed. Rare are other associated organ dysplasias (eyes, pancreas, intestine).

About 3-5% of MODY cases

Autosomal dominant mutations in the HNF1B gene located on chromosome 17 (17q12). The HNF1B gene encodes the transcription factor TCF2, which, among other things, regulates the transcription of genes involved in insulin production and secretion in pancreatic beta cells. The mutation leads to a pathologically reduced insulin production.

Diagnostic criteria for the majority of MODY 5 patients are: progressive hyperglycemia in old age; lean patients without type 1 diabetes; first manifestation in early adolescence (between 12-30 years of age); renal glucosuria, occurrence of diabetes in multiple generations and an overall severe disease course.

Common complications are retinopathies and kidney defects (renal hypoplasia, multicystic, dysplastic kidneys, cystic kidneys and single kidneys). The presence of diabetes and renal cysts is also summarized under the term RCAD = Renal Cysts and Diabetes. A part of the MODY 5 patients show malformations of the genitals (vaginal aplasia and uterine hypoplasia), gout or hyperuricemia.

MODY 5 patients show increased sensitivity to sulfonylureas and are usually well controlled with low drug doses over a prolonged period without insulin therapy.

Indication for the detection of MODY 5 gene mutation:

• Manifestation age in early adolescence
• no GAD and/or IA2 antibodies (exclusion of type 1 diabetes)
• Positive family history, autosomal dominant inheritance
• Diabetes without obesity
• Progressive hyperglycaemia in old age
• No insulin resistance
• Pancreatic aplasia with neonatal diabetes

1. Bingham C et al (2003) Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1-beta gene mutation. Kidney Int 63: 1645-1651
2. Furuta H et al (2002) Nonsense and missense mutations in the human hepatocyte nuclear factor-1-beta gene (TCF2) and their relation to type 2 diabetes in Japanese. J Clin Endocr Metab 87: 3859-3863
3. Wakayama M et al (2o10) HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatric nephrol 25:1073-1079
4. Lindner T et al (1999) A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1-beta. Hum Molec Genet 8: 2001-2008
5. Rebouissou S et al (2005) Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas. Hum Molec gene 14: 603-614