Mody 8E11.-

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).

In the very rare MODY 8 variant, mutations are present in the CEL gene, the carboxyl ester lipase gene located on chromosome 9q34.13 (Torsvik J et al. 2010), which codes for bile salt dependent lipase. This lipase is crucial for the exocrine function of the pancreas, but in the case of loss of function it also leads to a loss of endocrine activity of the pancreas. So far, only a few affected families have been identified (Hardt P D et al. 2003). A connection is being discussed with the mutation-induced dysfunction of carboxyl-ester lipase, chronic pancreatitis and pancreatic adenocarcinoma (Lombardo D et al. 2018).

A homozygous mutation leads to pancreatic aplasia and the pathologically decreased insulin production is clinically relevant. The inheritance is autosomal dominant.

<1% of MODY cases

Indication for the detection of MODY-8 gene mutations:

• 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. Hardt P D et al (2003) High prevalence of exocrine pancreatic insufficiency in diabetes mellitus: a multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients. Pancreatology 3: 395-402.
2. Lombardo D et al (2018) Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies? Oncotarget 9: 12513-12533.
3. Torsvik J et al (2010) Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes. Hum. Gene. 127: 55-64.