ARPKD is an autosomal recessive disease characterized by bilateral renal cystic enlargement that starts in utero. About 30% of patients die perinatally, although most patients reach ESRD in infancy, early childhood or adolescence.

Significantly enlarged polycystic kidneys are a hallmark of the disease. The liver is affected in approximately 45% of infants, and hepatic fibrosis is often the main feature in older patients.

Widening of collecting ducts in the kidney and intrahepatic bile ducts in the liver (Caroli disease) is seen at the histological level.

Epidemiology

 1/6000 to 1/14000 births.

Synopsis

 renal ARPKD

• normal nephrogenesis (nephron induction normal)with normal number of glomerules
• earliest lesions on medullary ducts with medullary collecting duct dilatation
• renal cysts (normal glomeruli and tubules are seen between cysts)
• dilatation of Bownan capsule with glomerular cysts
• radial elongated dilated tubules
• radial orientation of dilated tubules
• loss of corticomedullary differentiation
• slight interstitial renal fibrosis
• no significant renal interstitial inflammation

 oligohydramnios sequence (Potter sequence)

• Potter facies
• lung hypoplasia

 hepatic ARPKD

• congenital hepatic fibrosis
• hepatic cysts
• bile duct dilation
• ductal plate anomalies (congenital hepatic fibrosis)
• cirhhosis and cirrhotic sequence
  • splenomegaly
  • oesophageal varices

 pancreatic ARPKD

• pancreatic cysts

Etiology

 mutation in the gene PKHD1 encoding fibrocystin (MIM.606702 - Locus: 6p21.1-p12)

Pathogenesis

 Polycystic kidney and hepatic disease 1 (PKHD1) was identified by positional cloning and by the demonstration that mutations in its orthologue cause the renal cystic phenotype pck in the rat.

 PKHD1 encodes a novel protein, fibrocystin/polyductin, that has a role in terminal differentiation of the collecting duct and biliary systems - which explains the histological phenotype of patients with ARPKD.

 PKHD1 is also expressed in the primary cilia of renal epithelial cells. Although this is also the site of cystoprotein expression36, no protein interaction partners for PKHD1 have been identified so far in 2005.

Prognosis

 30 to 50% of affected individuals die in the neonatal period, while others survive into adulthood.

Nota bene: hepato-reno-pancreatic dysplasia has also been described as Ivemark syndrome (Ivemark II syndrome) or Caroli syndrome. This homonymy with the asplenic Ivemark syndrome (MIM.208530) encourages to avoid this name in this condition.

See also

 renal cysts
 cystic renal diseases
 polycystic kidney diseases (PKDs)

Differential diagnosis

 Meckel syndrome
 short rib-polydactyly syndromes
 multiple acyl-CoA dehydrogenation deficiency (MADD)(glutaric aciduria type 2)

References

 Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005 Dec;6(12):928-40. PMID: 16341073

 Nauli SM, Zhou J. Polycystins and mechanosensation in renal and nodal cilia. Bioessays. 2004 Aug;26(8):844-56. PMID: 15273987

 Lina F, Satlinb LM. Polycystic kidney disease: the cilium as a common pathway in cystogenesis. Curr Opin Pediatr. 2004 Apr;16(2):171-6. PMID: 15021197

 Wang S, Luo Y, Wilson PD, Witman GB, Zhou J. The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc Nephrol. 2004 Mar;15(3):592-602. PMID: 14978161

 Bendon RW. Ivemark's renal-hepatic-pancreatic dysplasia: analytic approach to a perinatal autopsy. Pediatr Dev Pathol. 1999 Jan-Feb;2(1):94-100. PMID: 9841713

 Strayer DS, Kissane JM. Dysplasia of the kidneys, liver, and pancreas: report of a variant of Ivemark's syndrome. Hum Pathol. 1979 Mar;10(2):228-34. PMID: 422192