Autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) is inherited in an autosomal recessive manner. This means that an affected individual has two gene alterations (mutations) in the PKHD1 gene, with one mutation inherited from each parent. Each parent, who has one altered copy of the gene, is referred to as a carrier. Carriers do not typically show signs and symptoms of the condition. When two carriers for an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be an unaffected carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier. This means that with each pregnancy, there is a 75% (3 in 4) chance to have an unaffected child.

The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy. Consideration of genetic counseling (including discussion of potential risks to offspring and reproductive options) is recommended for individuals who are affected, are carriers, or are at risk of being carriers.

Carrier testing for relatives of the affected individual is possible once the mutations have been identified in the family. If the disease-causing mutations in the PKHD1 gene cannot be identified, carrier detection using linkage analysis may be possible in families with at least one affected child and in which informative linked markers have been identified.

For high-risk pregnancies (i.e., those at 25% risk based on family history), prenatal testing for pregnancies at 25% risk is possible by analysis of DNA from fetal cells obtained by amniocentesis (usually performed at approximately 15 to 18 weeks gestation) or chorionic villus sampling (CVS), at approximately 10 to 12 weeks gestation. This is a means of finding out the genetic status of the fetus during the pregnancy. However, both disease-causing alleles (the two inherited mutations) of an affected family member must be identified, or linkage established, in the family before prenatal testing can be performed. There is currently no reliable available on the sensitivity and specificity of prenatal ultrasound examination in diagnosis of ARPKD in pregnancies at 25% risk.

As an alternative to prenatal diagnosis during the pregnancy, preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutations have been identified. Preimplantation diagnosis is used following in vitro fertilization to diagnose a genetic disease or condition in a preimplantation embryo (before it is introduced into the uterus). PGD allows prenatal testing to occur months earlier than conventional tests such as amniocentesis or CVS, even before a pregnancy begins. Doctors can test a single cell from an eight-cell embryo that is just days old. Individuals who may consider PGD include those at risk of transmitting a genetic disorder (such as ARPKD) to their offspring. The number of monogenic disorders (those caused by mutations in a single gene) that have been diagnosed in preimplantation embryos has increased each year. So far, hundreds of healthy babies have been born worldwide after undergoing the procedure, and the number is growing rapidly. Other things that may be determined during PGD are whether the embryo is a male or female, or whether it is carrying chromosomal abnormalities or rearrangements. PGD techniques have also been used to increase implantation rates, reduce the incidence of spontaneous abortion (miscarriage), and prevent offspring with trisomies (such as Down syndrome) in women of advanced maternal age undergoing fertility treatment.

For a list of laboratories offering PGD, click here.

Although a cure or treatment for the underlying genetic cause of autosomal recessive polycystic kidney disease does not exist, advancements have been made in showing improvement of liver and kidney disease in mouse models of the condition by disrupting the function of certain cell receptors.

Medical management is currently symptomatic and involves supportive care. Mechanical ventilation may be used to treat the underdevelopment of the lungs and breathing issues caused by the kidneys that are enlarged due to the numerous cysts. When the kidneys are severely enlarged, one or both kidneys may be removed (nephrectomy). Dialysis may be required during the first days of life if the infant is producing little urine (oliguria) or no urine (anuria). Low levels of sodium (hyponatremia) may occur and is treated with diuresis and/or sodium supplementation depending on the individual's specific levels. High blood pressure (hypertension) is treated with medication. Kidney failure requires dialysis, and kidney transplantation is another option. Poor eating and growth failure may be managed with gastrostomy tubes. Growth hormone therapy may be used to treat the growth failure and kidney insufficiency. Urinary tract infections are treated with antibiotics. Those with liver involvement may require shunt to treat the progressive high blood pressure and possibly liver transplantation.