Autosomal recessive polycystic kidney

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare, genetic disorder affecting the kidneys and liver. It is characterized by the development of numerous cysts in the kidneys, leading to renal enlargement and dysfunction. This condition is caused by mutations in the PKHD1 gene, which is responsible for the production of a protein called fibrocystin. ARPKD is a significant cause of kidney-related morbidity and mortality in infants and children.

Etiology

ARPKD is caused by mutations in the PKHD1 gene located on chromosome 6. This gene encodes fibrocystin, a protein thought to be involved in the development and function of the kidneys and liver. The disease is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Pathophysiology

The pathogenesis of ARPKD is closely related to the dysfunction of primary cilia, cellular structures that play a crucial role in the development and function of various organs, including the kidneys and liver. Mutations in the PKHD1 gene lead to abnormal fibrocystin, which disrupts the normal functioning of primary cilia, resulting in the formation of cysts in the kidneys and liver fibrosis.

Clinical Features

The clinical presentation of ARPKD can vary significantly among affected individuals. The most common symptoms include:

• Hypertension (high blood pressure)
• Renal insufficiency or failure
• Hepatomegaly (enlarged liver)
• Portal hypertension
• Respiratory distress in neonates due to enlarged kidneys

Diagnosis

Diagnosis of ARPKD is primarily based on clinical examination, family history, and imaging studies such as ultrasound, which can reveal enlarged kidneys with multiple cysts. Genetic testing for mutations in the PKHD1 gene can confirm the diagnosis.

Treatment

There is no cure for ARPKD, and treatment focuses on managing symptoms and complications. Treatment options may include:

• Antihypertensive medications to control high blood pressure
• Growth hormone therapy to address growth retardation
• Dialysis or kidney transplantation in cases of renal failure
• Management of liver-related complications, such as portal hypertension

Prognosis

The prognosis for individuals with ARPKD varies. Early diagnosis and management of hypertension and renal function can improve the quality of life and life expectancy. However, the disease can be severe, particularly in neonates and infants, where it can lead to significant morbidity and mortality.

Epidemiology

ARPKD is a rare disease, with an estimated incidence of 1 in 20,000 to 40,000 live births. It accounts for a significant proportion of childhood chronic kidney disease and renal failure.