Autosomal recessive polycystic kidney disease (ARPKD) is the recessive form of

polycystic kidney disease Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These c ...

. It is associated with a group of congenital fibrocystic syndromes. Mutations in the ''

PKHD1 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 ...

'' (chromosomal locus 6p12.2) cause ARPKD.

Signs and symptoms

Symptoms and signs include

abdominal discomfort Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a more ...

polyuria Polyuria () is excessive or an abnormally large production or passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed diuresis. Polyuria often appears in conjunction wit ...

polydipsia Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives from the Greek () "very thirsty", which is derived from (, "mu ...

, incidental discovery of hypertension, and

abdominal mass An abdominal mass is any localized enlargement or swelling in the human abdomen. Depending on its location, the abdominal mass may be caused by an enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), protruding kidney, a pancreatic m ...

. The classic presentation for ARPKD is systemic hypertension with progression to

end-stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

(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 and as a result, may present with

Potter sequence Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. Oligohydramnios is the decr ...

.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 /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 In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progres ...

and

mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...

and may regulate centrosome duplication and mitotic spindle assembly during

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

. 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 In medical genetics, compound heterozygosity is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state; that is, an organism is a compound heterozygote when it ...

for PKHD1 mutations. Patients with two

nonsense mutation In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a ''nonsense codon'' in the transcribed mRNA, and in leading to a truncated, incomplete, and usually nonfunctional protein produc ...

s appear to have an earlier onset of the disease.

Diagnosis

Ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

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, wh ...

* Diffuse cystic dysplasia

Treatment

The treatment options for autosomal recessive polycystic kidney disease, given there is no current cure, are: * Medications for hypertension * Medications and/or surgery for pain *

Antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

for infection * Dialysis (if

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

is present) * Kidney transplantation(in serious cases)

References

External links

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