autosomal recessive polycystic kidney disease, PKHD1-related Carrier Screening (Genetic Testing) Overview

What is Autosomal Recessive Polycystic Kidney Disease, PKHD1-related?

Autosomal recessive polycystic kidney disease, PKHD1-related (ARPKD) is a genetic condition that primarily affects the kidneys and liver. It is caused by harmful genetic changes (variants) in the PKHD1 gene, which provides instructions for making a protein called fibrocystin. This protein plays a key role in the normal development and function of kidney and liver cells. When fibrocystin is absent or not working properly, it disrupts how these organs grow and function.

Individuals with ARPKD typically develop numerous fluid-filled sacs (cysts) in their kidneys. These cysts can impair the kidneys’ ability to filter waste from the blood, potentially leading to kidney failure. Cysts may also form in the liver and in the bile ducts—small tubes that carry bile through the digestive system. High blood pressure (systemic hypertension) is commonly seen. Liver involvement can include enlargement (hepatomegaly) and the development of scar tissue (congenital hepatic fibrosis), due to abnormal formation of blood vessels and bile ducts. Liver complications may lead to increased pressure in the liver’s blood vessels (portal hypertension), an enlarged spleen (splenomegaly), low blood cell counts (thrombocytopenia), and internal bleeding from swollen veins (varices) in the esophagus or stomach. Additionally, the bile ducts may become enlarged and more prone to infection (cholangitis).

ARPKD is grouped into three forms based on when symptoms first appear: perinatal, infantile, and childhood/young adult.

Perinatal form

This form of ARPKD presents symptoms before a baby reaches 4 weeks of age. In many cases, signs are detected on ultrasound during pregnancy, which may show enlarged kidneys and little or no amniotic fluid. After birth, affected infants may experience serious lung complications, including underdeveloped lungs and narrowed blood vessels that limit oxygen flow (persistent pulmonary hypertension). Feeding difficulties and poor growth are also common.

Infantile form

Symptoms of ARPKD in this form typically appear between 4 weeks and 1 year of age. Compared to the perinatal form, lung complications are less common.

Childhood/young adult form

In this form of ARPKD, symptoms begin after the first year of life. Liver complications are more frequent and severe in this form. There are no lung problems, and kidney problems tend to be milder.

Additional considerations for carriers

Carriers may have a slightly higher chance of developing a small number of kidney or liver cysts. It is thought that these cysts don't cause symptoms in most people, though more research is needed to confirm.

How common is Autosomal Recessive Polycystic Kidney Disease, PKHD1-related?

There are several genes that cause ARPKD, which has an incidence of approximately 1 in 20,000 to 1 in 30,000 births. Approximately 85% of ARKPD is caused by PKHD1. The incidence of ARPKD caused by PKHD1 is more common among individuals of Afrikaner and Ashkenazi Jewish descent. 

How is Autosomal Recessive Polycystic Kidney Disease, PKHD1-related treated?

There is currently no cure for ARPKD, but treatments can help manage symptoms. Infants with lung problems may need breathing support. If the kidneys fail, treatments like dialysis (a machine that cleans the blood) or a kidney transplant may be needed. In cases of severe liver disease, a liver transplant might also be recommended. Other treatments can include medications for high blood pressure or infections, nutritional support, and growth hormone therapy.

What is the prognosis for an individual with Autosomal Recessive Polycystic Kidney Disease, PKHD1-related?

About 20% of babies with ARPKD die in the first year of life due to lung complications. For those who survive past infancy, about 80% are still alive at age 10. Around half of all individuals will experience kidney failure by age 20. With advances in organ transplantation and medical care, people with ARPKD may live longer lives.

Benefits of autosomal recessive polycystic kidney disease, PKHD1-related Carrier Screening (Genetic Testing)

Carrier screening is an important form of genetic testing for those who may be at risk of passing autosomal recessive polycystic kidney disease, pkhd1-related to their baby. Carrier Screening for autosomal recessive polycystic kidney disease, pkhd1-related can help in identifying that risk. The Foresight^® Carrier Screen helps clinicians guide care and empowers patients to take action to make the best decision for their families. Learn more about the Foresight^® Carrier Screen} by Myriad Genetics.