Autosomal Recessive Polycystic Kidney Disease (ARPKD), Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Autosomal recessive polycystic kidney disease (ARPKD) is a disorder caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene. The incidence of ARPKD is approximately 1:20,000 and the estimated carrier frequency in the general population is 1:70. ARPKD is characterized by enlarged echogenic kidneys, congenital hepatic fibrosis, and pulmonary hypoplasia (secondary to oligohydramnios [insufficient volume of amniotic fluid] in utero). Most individuals with ARPKD present during the neonatal period, and of those, nearly one third die of respiratory insufficiency. Early diagnosis, in addition to initiation of renal replacement therapy (dialysis or transplantation) and respiratory support, increases the 10-year survival rate significantly. Presenting symptoms include bilateral palpable flank masses in infants and subsequent observation of typical findings on renal ultrasound, often within the clinical context of hypertension and prenatal oligohydramnios. In rarer cases, individuals may present during childhood or adulthood with hepatosplenomegaly. Of those who survive the neonatal period, one third progress to end-stage renal disease and up to half develop chronic renal insufficiency.
The PKHD1 gene maps to 6p12 and includes 67 exons. The PKHD1 gene encodes a protein called fibrocystin, which is localized to the primary cilia and basal body of renal tubular and biliary epithelial cells. Because ARPKD is an autosomal recessive disease, affected individuals must carry 2 deleterious mutations within the PKHD1 gene. Although disease penetrance is 100%, intrafamilial variation in disease severity has been observed.
Carrier testing of individuals for ARPKD when familial mutations have been previously identified
Diagnostic confirmation of autosomal recessive polycystic kidney disease when familial mutations have been previously identified
Prenatal diagnosis when 2 familial mutations have been previously identified in an affected family member
An interpretative report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order ARPKD / Autosomal Recessive Polycystic Kidney Disease (ARPKD), Full Gene Analysis.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with polycystic kidney disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Guay-Woodford LM, Desmond RA: Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics 2003;111:1072-1080
2. Gunay-Aygun M, Avner E, Bacallao RL, et al: Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary of a first National Institutes of Health/Office of Rare Diseases conference. J Pediatr 2006;149:159-164
3. Harris PC, Rossetti S: Molecular genetics of autosomal recessive polycystic kidney disease. Mol Genet Metab 2004;81:75-85