Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5)

Area of Science:

• Genetics
• Endocrinology
• Hepatology

Background:

• Maturity-onset diabetes of the young type 5 (MODY 5) is a genetic disorder caused by mutations in the HNF1B gene.
• HNF1B mutations are associated with insulin resistance, young-onset diabetes, and potential multi-organ involvement.
• The renal cyst and diabetes syndrome is an autosomal dominant condition linked to HNF1B gene variants.

Observation:

• This case report details a family with MODY 5 exhibiting unexplained elevated liver enzymes.
• The affected family members, including siblings and their mother, carried a specific HNF1B gene point mutation (p.Arg235Trp) at chromosome 17q12.
• No other clear etiology was identified for the increased liver enzymes in these individuals.

Findings:

• A heterozygous point mutation, p.Arg235Trp, in the HNF1B gene was identified in affected family members.
• This specific HNF1B variant is confirmed to be associated with autosomal dominant MODY 5 and renal cysts.
• The study observed a correlation between this HNF1B mutation and elevated liver enzymes in the absence of other known causes.

Implications:

• This finding expands the known clinical spectrum of HNF1B-associated MODY 5 to include unexplained hypertransaminasemia.
• Early genetic testing for HNF1B mutations may be beneficial for families with a history of diabetes and unexplained liver enzyme elevations.
• Understanding the pleiotropic effects of HNF1B mutations is crucial for comprehensive patient management and genetic counseling.