HNF1beta associated (kidney) disease / ADTKD-HNF1b

This disease is caused by a defect (mutation) in the genetic material (DNA). Mutations in one of the two HNF1b genes lead to disorders and symptoms of the kidney and other organs. HNF1b plays an important role in the development of the kidneys and affects the function of  important transport proteins in the kidney tubules.
Signs and symptoms
Due to a mutation in a HNF1b gene, the normal development and function of various organs is disturbed. This may cause renal cysts and renal function disorders. Congenital renal abnormalities may also occur, such as having one kidney instead of 2 kidneys, small kidneys or a disturbed shape of the kidney. These congenital kidney abnormalities usually lead to decreased kidney function, which again can cause problems. In addition, urinary loss of magnesium may occur, resulting in a low magnesium level in the blood. A reduced level of magnesium may result in different symptoms such as muscle weakness and muscle twitches / contractions. Due to a disturbed construction and / or function of the pancreas, there is an increased risk of diabetes mellitus, often at a relatively young age. Furthermore, the parathyroid glands may produce too much parathyroid hormone and there is an increased risk of gout. The occurrence and severity of the different abnormalities may vary from person to person, even within one family.

HNF1b-related (kidney) disease is a disease which is inherited autosomal dominant. This means that a person will have this condition if he or she is has a mutation in one HNF1b gene. Not all patients, however, have inherited the mutation from their parents. A portion of the patients have a new mutation. A son or daughter of someone with the disease has a chance to inherit the disease with a probability of 50%.

The diagnosis HNF1b-related disease can be confirmed by a test in which a genetic mutation in the HNF1b gene is demonstrated in a patient who has characteristics of the disease.

There is no causal treatment available to treat the underlying disorder. In other words, the dysfunctional HNF1b gene cannot be repaired. The treatment, therefore, consists of the treatment of the disturbed (organ) functions. Diabetes is treated with drugs to normalize blood sugar levels and magnesium tablets are given in case of a low magnesium level.

HNF1b-related (kidney) disease is a chronic condition, which means that it persists lifelong. Not much is known about the prognosis and, moreover, it differs between individuals, even within families with the same mutation HNF1b. It is known that most of patients have demonstrated a slow deterioration of the renal function, wherein a portion of the patients renal failure develops, for which ultimately renal replacement therapy (dialysis, renal transplantation) is necessary.