Mody 11 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).

The very rare MODY 11 is caused by monogenic, autosomal-dominantly inherited mutations in the BLK gene located on the short arm of chromosome 8p23.1. The BLK gene encodes a transcription factor (B-lymphocytic tyrosine kinase), which regulates the transcription of genes involved in insulin production and secretion in pancreatic beta cells. Mutations in the BLK gene lead to pathologically decreased insulin production. Furthermore, the mutations lead to malfunctions of various pancreatic enzymes (e.g. pancreatic lysophospholipase).

Clinically, the majority of MODY 11 patients have the following clinical features: early age of onset (usually <25 years), overall mild clinical course, hyperglycemia; slim patients without type 1 diabetes; occurrence of diabetes in several generations, although missing diabetes cases in the family do not rule out MODY 11, as diabetes is often not detected. The percentage of BLK gene mutations in all MODY patients is estimated to be approximately <1%.

Characteristic features of MODY 11 include the absence of autoimmune phenomena (no detection of GAD-AK and IA2-AK). Gene analysis provides a reliable confirmation of the clinical suspicion so that an appropriate therapy can be initiated.

1. Islam KB et al (1995) Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk.J Immunol 154:1265-1272.
2. Zhang H et al (2012) The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells. Nature Genet 44: 861-871