Mody 13E11.-

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).

MODY 13 is caused by heterozygous mutations in the KCNJ11 gene (Potassium Voltage-Gated Channel Subfamily J Member 11) located on chromosome 11p15 and encoding KIR6.2, a subunit of the ATP-sensitive potassium channel.

Mody13- patients are usually characterized by an increasingly severe clinical course. They are slim patients without type 1 diabetes. The first manifestation of the familial diabetes occurs in early adolescence (between 12-30 years); renal glucosuria persists. If left untreated, MODY 13 patients develop almost all late complications that can also be observed in type 2 diabetics (diabetic angiopathy, neuropathy, nephropathy).

MODY 13 patients, like other MODY variants, respond excellently to therapy with low-dose sulfonylureas (see Bonnefond et al. 2012; Yorifuji et al. 2005). In advanced age, insulin therapy becomes necessary in about one in three patients. Note: This statement is also true for MODY variants 1,3, 12. These are genotypically different, but phenotypically largely the same with progressive hyperglycemia.

Bonnefond et al (2012) described a French family over 4-generation family with 12 members affected by MODY. The diagnosis age was between 13 and 59 years. In addition, one member had impaired fasting glucose and another member had impaired glucose tolerance. No family member had neonatal diabetes mellitus (NDM). A mutation in the KCNJ11 gene was detected. Affected individuals were effectively treated with oral sulfonylureas, which confirmed the phenotype as MODY13. The age at diagnosis of diabetes was between 13 and 59 years.

Yorifuji et al (2005) described a Japanese family over 4 generations with diabetes mellitus. The age at diagnosis of the 4 affected persons was between 3 and 26 years. One patient suffered from one in childhood; 2 had adult type 2 diabetes. A Cys42-Arg mutation was found in the KCNJ11 gene. 2 of the 4 affected persons controlled their diabetes exclusively with sulfonylureas.

1. Bonnefond A et al (2012) Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 7: e37423
2. Yorifuji T et al (2005) The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus. J. Clin. Endocr. Metab 90: 3174-3178