Dent's disease

Dent's Disease is a rare, genetic disorder primarily affecting the kidneys. It is characterized by symptoms such as low molecular weight proteinuria, hypercalciuria, kidney stones, nephrocalcinosis, and progressive renal failure. This condition is part of a group of diseases known as tubulopathies, which affect the renal tubules of the kidneys. Dent's Disease is caused by mutations in the CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes, leading to dysfunction in the protein products these genes encode. The disease predominantly affects males, but female carriers may exhibit milder symptoms.

Symptoms and Diagnosis

The primary symptom of Dent's Disease is low molecular weight proteinuria, which is the excessive excretion of proteins in the urine. Other common symptoms include hypercalciuria (high levels of calcium in the urine), the formation of kidney stones (nephrolithiasis), and nephrocalcinosis (calcium accumulation in the kidneys). These symptoms can lead to chronic kidney disease and, ultimately, end-stage renal disease (ESRD).

Diagnosis of Dent's Disease is based on clinical findings, family history, and genetic testing. The presence of the hallmark symptoms, especially when combined with a family history of similar issues, can prompt further investigation through genetic testing to identify mutations in the CLCN5 or OCRL genes.

Genetics

Dent's Disease is inherited in an X-linked recessive pattern. The condition is caused by mutations in either the CLCN5 gene (Dent disease 1), which is located on the X chromosome and encodes a chloride channel protein, or the OCRL gene (Dent disease 2), which also resides on the X chromosome and encodes an inositol polyphosphate 5-phosphatase. These mutations disrupt the normal function of the proteins involved in renal tubular reabsorption, leading to the symptoms observed in affected individuals.

Treatment and Management

There is no cure for Dent's Disease, and treatment focuses on managing symptoms and slowing the progression of kidney damage. Management strategies may include hydration to prevent kidney stones, medications to reduce calcium levels in the urine, and monitoring for progression of kidney disease. In advanced cases, renal replacement therapy such as dialysis or kidney transplantation may be necessary.

Prognosis

The prognosis for individuals with Dent's Disease varies. Some affected individuals may have a relatively mild course with few complications, while others may develop progressive renal failure requiring renal replacement therapy. Early diagnosis and management are crucial in improving the quality of life and slowing the progression of kidney damage.

See Also

• Kidney stone
• Nephrocalcinosis
• Chronic kidney disease
• Genetic testing
• X-linked recessive inheritance