Maturity Onset Diabetes of the Young 5

Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.

Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians.

The summary below is from the full report titled "Clinical Spectrum Associated with Hepatocyte Nuclear Factor-1ß Mutations." It is in the 6 April 2004 issue of Annals of Internal Medicine (volume 140, pages 510-517). The authors are C. Bellanné-Chantelot, D. Chauveau, J.-F. Gautier, D. Dubois- Laforgue, S. Clauin, S. Beaufils, J.-M. Wilhelm, C. Boitard, L.-H. Noël, G. Velho, and J. Timsit.

What is the problem and what is known about it so far?

Maturity-onset diabetes of the young (MODY) is caused by a genetic change (mutation) that reduces insulin production and raises the blood sugar level. Most people with MODY become diabetic before age 25 years. Several types of MODY are caused by different gene mutations. The severity of the diabetes depends on the type of MODY. One type, known as MODY5, results from a mutation in the hepatocyte nuclear factor-1 (HNF-1) gene. People with MODY5 may have kidney disease, although not the type that is typical for diabetes. Some also may have malformed genital organs. However, MODY5 is uncommon, and few studies describe the clinical and genetic findings associated with the disease.

Why did the researchers do this particular study?

To describe clinical and genetic findings in people with HNF-1 mutations and MODY5.

Who was studied?

13 patients from 8 unrelated families who had HNF-1 mutations. Eight patients were the first in their families found to have a mutation, and 5 patients were offspring who had inherited a mutation.

How was the study done?

The researchers recruited patients with HNF-1 mutations or diabetes that occurred at an early age and abnormal kidneys from 4 medical departments. They examined patients' kidneys by using ultrasounds, computed tomography scans, or x-rays after injecting a dye. They also measured each patient's kidney function and took small pieces (biopsy specimens) of each patient's kidney tissue. They performed ultrasounds to look for genital tract abnormalities and computed tomography scans to examine the pancreas. They also took blood samples to measure levels of insulin and liver function and to analyze DNA.

What did the researchers find?

Ten of the 13 patients were diabetic, but half of them had no diabetic symptoms at diagnosis. Six patients required insulin treatment. Most had kidneys that were small or contained cysts, and most had kidney failure. About half had small, withered pancreases. Five patients had abnormal genital organs, and 5 patients had abnormal liver function test results. Finally, the DNA analysis showed several different types of mutations of the HNF-1 gene in the patients.

What were the limitations of the study?

The study included few patients who were being followed in 4 clinics. Characteristics of these few selected patients may not be the same as those found in most patients with MODY5.

What are the implications of the study?

Maturity-onset diabetes of the young 5 is an uncommon disease that has diverse clinical and genetic findings.