Autosomal recessive polycystic kidney disease

A genetic disorder affecting the kidneys and liver

Adenine phosphoribosyltransferase deficiency
Dihydroxyadenine.png
Dihydroxyadenine, an insoluble purine
Synonyms	APRT deficiency, 2,8-Dihydroxyadenine urolithiasis
Specialty	Nephrology, Genetics
Symptoms	Hematuria, kidney stones, flank pain, urinary tract obstruction
Complications	Chronic kidney disease, nephrolithiasis, renal failure
Usual onset	Childhood or early adulthood
Duration	Lifelong
Types	Type I (complete enzyme deficiency), Type II (residual activity)
Causes	Mutation in the APRT gene (autosomal recessive)
Risk factors	Family history, consanguinity
Diagnosis	Stone analysis, urinary dihydroxyadenine crystals, genetic testing, enzyme assay
Differential diagnosis	Uric acid stones, xanthinuria, cystinuria
Prevention	Early diagnosis and treatment
Treatment	High fluid intake, low purine diet, urine alkalinization
Medication	Allopurinol, febuxostat
Prognosis	Good with early diagnosis and lifelong treatment
Frequency	Rare (estimated <1:100,000 worldwide)
Deaths	Rare; related to renal complications if untreated

Autosomal recessive polycystic kidney disease with a normal kidney inset

Micrograph of von Meyenburg complex.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the development of cysts in the kidneys and liver. It is an inherited condition that follows an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease.

Pathophysiology

ARPKD is caused by mutations in the PKHD1 gene, which encodes the protein fibrocystin/polyductin. This protein is involved in the normal development and function of the kidneys and bile ducts. Mutations in the PKHD1 gene lead to the formation of numerous small cysts in the renal tubules and bile ducts, resulting in impaired kidney and liver function.

Clinical Presentation

The clinical manifestations of ARPKD can vary widely, but they typically present in infancy or early childhood. Common symptoms include:

• Enlarged kidneys (nephromegaly)
• Hypertension
• Renal insufficiency
• Hepatomegaly
• Portal hypertension
• Respiratory distress in newborns due to enlarged kidneys compressing the lungs

Diagnosis

Diagnosis of ARPKD is based on clinical findings, family history, and imaging studies. Ultrasound is the primary imaging modality used to identify the characteristic cystic changes in the kidneys and liver. Genetic testing can confirm the diagnosis by identifying mutations in the PKHD1 gene.

Management

There is no cure for ARPKD, and treatment is primarily supportive. Management strategies include:

• Control of blood pressure with antihypertensive medications
• Monitoring and management of renal function
• Treatment of liver complications, such as portal hypertension
• Dialysis or kidney transplantation in cases of end-stage renal disease

Prognosis

The prognosis for individuals with ARPKD varies depending on the severity of the disease. Some infants may experience severe complications shortly after birth, while others may have a milder course and survive into adulthood. Early diagnosis and management of complications can improve outcomes.

Genetic counseling

Genetic counseling is recommended for families affected by ARPKD. Since the condition is inherited in an autosomal recessive manner, there is a 25% chance with each pregnancy that an affected couple will have a child with the disease.

Related pages

• Polycystic kidney disease
• Autosomal dominant polycystic kidney disease
• Genetic disorders
• Kidney disease