From the Guidelines
HNF-1b MODY is a genetic form of diabetes caused by mutations in the hepatocyte nuclear factor-1 beta gene, characterized by developmental renal disease, genitourinary abnormalities, atrophy of the pancreas, hyperuricemia, and gout, and is typically managed with sulfonylureas, with insulin therapy often required over time 1.
Key Features of HNF-1b MODY
- Developmental renal disease (typically cystic)
- Genitourinary abnormalities
- Atrophy of the pancreas
- Hyperuricemia
- Gout
Diagnosis and Management
- Genetic testing is crucial for diagnosis
- Family screening is recommended due to autosomal dominant inheritance pattern
- Treatment usually begins with sulfonylureas, but many patients eventually require insulin therapy
- Regular monitoring of kidney function, liver enzymes, and pancreatic exocrine function is essential
Clinical Considerations
- Metformin is generally avoided due to the risk of lactic acidosis in patients with kidney dysfunction
- Patients may develop complications in the kidneys, liver, and pancreas, emphasizing the need for regular monitoring
- Genetic counseling is recommended to ensure affected individuals understand the patterns of inheritance and the importance of a correct diagnosis
Recent Guidelines
- The most recent guidelines from 2025 recommend considering a diagnosis of MODY in individuals with atypical diabetes and multiple family members with diabetes not characteristic of type 1 or type 2 diabetes 1
- Genetic screening is increasingly available and cost-effective, and consultation with a center specializing in diabetes genetics is recommended 1
From the Research
Definition and Characteristics of HNF-1b MODY
- HNF-1b MODY, also referred to as "renal cysts and diabetes syndrome" or MODY-5, is a rare form of monogenic diabetes caused by a deletion or point mutation in the HNF1B gene 2.
- This gene plays a key role in regulating urogenital and pancreatic development, and mutations in it can lead to renal, hepatic, and other extrapancreatic features 2, 3.
- HNF1B-MODY is characterized by its association with renal disease, and patients with this condition often present with early-onset diabetes and renal anomalies 3.
Clinical Presentation and Diagnosis
- The clinical presentation of HNF1B-MODY can be similar to that of type 1 or type 2 diabetes, making diagnosis challenging 2, 4.
- A timely diagnosis of HNF1B-MODY is crucial, as it can greatly impact diabetes management and disease progression, as well as family history 2.
- Genetic testing is essential for definitive diagnosis, and scanning non-coding regions is important to avoid missing a mutation in the HNF1B gene 3.
Treatment and Management
- Treatment options for HNF1B-MODY are limited, and more research is needed to develop effective management strategies 5.
- Patients with HNF1B-MODY may require individualized treatment plans, taking into account their specific clinical characteristics and genetic mutations 5, 6.
- Sulphonylureas may be effective in managing blood glucose levels in patients with HNF1B-MODY, but caution is needed due to the risk of hypoglycemia 6.