Dent and Lowe disease
The Dent’s disease is a rare condition with a disturbance in the function of the kidney tubules causing problems with retention of salts, minerals and proteins. The disease is caused by defect (mutation) in the genetic material (DNA). Due to such a mutation, specific cells of the renal tubules which reabsorb proteins and minerals such as calcium, cannot function properly.
Signs and symptoms
A mutation in either the CLCN5 or the OCRL1 gene causes a disturbance in the function of the first part of the renal tubule. The (male) patients loose too much small proteins and calcium in their urine, due to which they can develop calcium deposits in the kidneys, kidney stones, kidney failure and rickets (rickets). In addition, patients often suffer from too much urination and an increased excretion of phosphate, sugar and amino acids in the urine. Patients with a mutation in OCRL1 also have trouble excreting acid, develop cataracts at a young age and often have mental retardation. This disease is also known as Lowe disease or oculocerebrorenaal syndrome.
Dent’s and Lowe disease are hereditary diseases. The genes CLCN5 and OCRL1 are located on the X chromosome. Dent’s disease and Lowe disease inherit X-linked. Men have an X and a Y chromosome. Women have two X chromosomes. This means that women have the disease only when the DNA abnormality is present on both X chromosomes and men have the disease when their single X chromosome is abnormal. Women with a mutation at a single X chromosome are called carriers, they usually do not develop symptoms of the disease. Sisters of patients with the disease of Dent or Lowe may therefore be a possible carrier, and can transmit the disease. A son has a 50% chance of the disease and a daughter 50% chance of being a carrier. Brothers of patients with these diseases, have a great chance to have the disease (50%).
The diagnosis is made on the basis of clinical symptoms, and confirmed with a genetic test. However, not all patients turn out to have a mutation with genetic testing.
There is no causal treatment available to treat the underlying disorder. In other words, the dysfunctional part of the renal tubule cannot be repaired. Treatment consists mainly of reducing calcium excretion in the urine and preventive measures to prevent stone formation. This is often done with a salt restriction and thiazide diuretics.
The prognosis is mainly determined by kidney function. Two thirds of patients develop severe kidney failure at the age of 30-40 years, and ultimately require renal replacement therapy in the form of dialysis or kidney transplantation.