PCLD1 is a disorder characterized by the presence of multiple fluid filled cysts throughout the liver. The cysts are of biliary epithelial origin and result in abdominal distention, back pain, dyspnea and early satiety. In rare cases, infection, rupture or haemorrhage of cysts may occur or hepatic venous outflow may be obstructed. Other anomalies may include lower triglycerides and total cholesterol, and higher levels of total bilirubin and serum alkaline phosphatase. The disease does not extend to the kidneys and patients do not have renal cysts. The disorder has an overall incidence of 1 in 100,000 individuals. It disproportionately affects females compared to males. Also, affected women are seen to have a larger number of cysts than affected men. The disorder has an onset after 40 years of age and increases in severity over time. However, some affected individuals may remain asymptomatic and do not require any treatment.
Diagnosis is made based on ultrasound and MRI imaging studies. The criteria for a PCLD diagnosis, for a person with no known family history of disease, is having more than 20 cysts. In members of affected families, the minimum requirement is having more than one cyst in patients below the age of 40 and more than three cysts in patients above 40 years. Somatostatin analogues such as lanreotide and long acting octreotide have been found to be effective in controlling cystic growth. Other treatment options may include percutaneous cyst aspiration, cyst fenestration, partial hepatectomy and liver transplantation in severe cases.
The disorder follows an autosomal dominant pattern of inheritance and is caused by heterozygous mutations in the PRKCSH gene. This gene encodes the non-catalytic beta subunit of Glucosidase II, an enzyme involved in N-linked glycan processing in the endoplasmic reticulum. Several PRKCSH gene mutations have been identified in PCLD1 affected individuals. These include splice site mutations, insertions and transitions that result in premature termination.
Monies et al. (2017) analyzed the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 3-year-old male, presented with unexplained chronic liver failure and hyperbilirubinemia and was being considered for a liver transplant. Using a multigene panel for gastrointestinal disorders, a heterozygous mutation (c.1462-1G>C) was identified in exon 17 of the patient’s PRKCSH gene, associated with PCLD1. Identification of this mutation was very beneficial as it allowed the researchers to select an unaffected donor relative for the transplant. Further, as the patient had no cysts on ultrasonography, this case was representative of an atypical polycystic liver disease phenotype.
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