Test ID ARPKZ Autosomal Recessive Polycystic Kidney Disease (ARPKD), Full Gene Analysis

Useful For

Diagnosis of individuals suspected of having autosomal recessive polycystic kidney disease (ARPKD)

Prenatal diagnosis if there is a high suspicion of ARPKD based on ultrasound findings

Carrier testing of individuals with a family history of ARPKD but an affected individual is not available for testing or disease-causing mutations have not been identified

Reflex Tests

Test ID	Reporting Name	Available Separately	Always Performed
CULFB	Fibroblast Culture for Genetic Test	Yes	No
CULAF	Amniotic Fluid Culture/Genetic Test	Yes	No
MATCC	Maternal Cell Contamination, B	Yes	No

Testing Algorithm

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

Special Instructions

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequencing Analysis

(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Reporting Name

ARPKD Full Gene Analysis

Specimen Type

Varies

Forms:

1. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Specimen preferred to arrive within 96 hours of collection.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Specimen Minimum Volume

Blood: 1 mL/Amniotic Fluid: 10 mL/Chorionic Villi: 5 mg

Specimen Stability Information

Specimen Type	Temperature	Time
Varies	Varies

Clinical Information

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 one-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. Mutation detection is often difficult due to the large gene size and the prevalence of private mutations that span the entire length of the gene.

Reference Values

An interpretive report will be provided.

Cautions

A small percentage of individuals who are carriers or have a diagnosis of autosomal recessive polycystic kidney disease (ARPKD) may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of ARPKD. For carrier testing, it is important to first document the presence of a polycystic kidney and hepatic disease 1 (PKHD1) gene mutation in an affected family member.

In some cases, DNA alterations of undetermined significance may be identified.

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

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.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Day(s) Performed

Performed weekly; Varies

Report Available

14 days

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81408-Unlisted molecular pathology procedure

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

Amniotic Fluid Culture/Genetic Test

88235-Tissue culture for amniotic fluid (if appropriate)