Autosomal recessive polycystic kidney disease (ARPKD) is the recessive form of polycystic kidney disease. It is associated with a group of congenital fibrocystic syndromes. Mutations in the '' PKHD1'' (chromosomal locus 6p12.2) cause ARPKD.

Signs and symptoms

Symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an disease, illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormali ...

and

signs Signs may refer to: * ''Signs'' (2002 film), a 2002 film by M. Night Shyamalan * ''Signs'' (TV series) (Polish: ''Znaki'') is a 2018 Polish-language television series * ''Signs'' (journal), a journal of women's studies *Signs (band), an American ...

include abdominal discomfort, polyuria, polydipsia, incidental discovery of

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, and abdominal mass. The classic presentation for ARPKD is systemic hypertension with progression to end-stage kidney disease (ESKD) by the age of 15. In a typical presentation, a small number of individuals with ARPKD live to adulthood with some kidney function; but with significant deterioration in liver function. This outcome is postulated to result from expression of the polycystic kidney and hepatic disease gene PKHD1, which is located on chromosome 6p. In severe cases, a fetus will present with

oligohydramnios Oligohydramnios is a medical condition in pregnancy characterized by a deficiency of amniotic fluid, the fluid that surrounds the fetus in the abdomen, in the amniotic sac. It is typically diagnosed by ultrasound when the amniotic fluid index (A ...

and as a result, may present with Potter sequence.Shastry SM, Kolte SS, Sanagapati PR. Potter's Sequence. J Clin Neonatol. 2012 Jul;1(3):157-9. doi: 10.4103/2249-4847.101705. PMID 24027716; PMCID: PMC3762025.

Genetics

The cause of ARPKD is linked to mutations in the PKHD1 gene. PKHD1 gene codes forfibrocystin. Fibrocystin is found in the epithelial cells of both the renal tubule and the bile ducts; deficiency leads to the characteristic polycystic dilation of both structures ARPKD is a significant hereditary renal disease in that appears in childhood. The prevalence is estimated to be of 1 in 20,000 live births, with a reported carrier frequency of up to 1:70. The single gene mutation called ''PKHD1'' is fully responsible for the disease presentation of ARPKD. This PKHD1 is located on the human chromosome region 6p21.1–6p12.2. It is also one of the largest genes in the genome as it occupies approximately 450 kb of DNA, and contains at least 86 exons. It is capable of producing multiple alternatively spliced transcripts. The largest known transcript encodes

fibrocystin Fibrocystin is a large, receptor-like protein that is thought to be involved in the tubulogenesis and/or maintenance of duct-lumen architecture of epithelium. FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd ...

/polyductin (FPC), which is a large receptor-like integral membrane protein of 4074 amino acids. The structure of the FPC consist of a single transmembrane, a large N-terminal extracellular region, and a short intracellular cytoplasmic domain. The FPC protein is found on the primary cilia of epithelia cells of cortical and medullary collecting ducts and cholangiocytes of bile ducts, and show similarity to polycystins and several other ciliopathy proteins. FPC is also found to be expressed on the basal body and plasma membrane. It is presumed that the large extracellular domain of FPC binds to a ligand(s) that is yet unknown and that is also involved in cell-cell and cell-matrix interactions. It is known that FPC interacts with ADPKD protein PC2 and may also participate in this regulation pathway of the mechanosensory function of the primary cilia, calcium signaling, and PCP. This is suggesting a common mechanism underlying cystogenesis between ADPKD and ARPKD. The FPC protein is also found on the centrosomes and mitotic spindle and may regulate centrosome duplication and mitotic spindle assembly during cell division. There have been a large number of various single-gene mutations found throughout PKHD1 and are unique to individual families. Most of the patients are compound heterozygotes for PKHD1 mutations. Patients with two nonsense mutations appear to have an earlier onset of the disease.

Diagnosis

Ultrasonography is the primary method to evaluate autosomal recessive polycystic kidney disease, particularly in the perinatal and neonatal stages.

Differential diagnosis

The differential diagnoses of this condition include: * Glomerulocystic kidney disease *

Autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, whi ...

* Diffuse cystic dysplasia

Treatment

The treatment options for autosomal recessive polycystic kidney disease, given there is no current cure, are: * Medications for

* Medications and/or surgery for pain * Antibiotics for infection *

Dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...

(if kidney failure is present) *

Kidney transplantation Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...

(in serious cases)

References

External links

{{DEFAULTSORT:Autosomal Recessive Polycystic Kidney Ciliopathy Kidney diseases Rare diseases