Search

Cystic fibrosis (CF) is a multisystem disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR is expressed in the apical surface of cholangiocytes. Homozygous CFTR gene mutation results in viscous and acidic bile secretions secondary to deficient surface fluid and bicarbonate efflux. Viscous, inspissated bile causes ductular obstruction and hepatotoxicity from retained bile components, leading to fibrosis and ultimately cirrhosis, known as CF liver disease (CFLD). CFLD is the third leading cause of death in CF patients. CFLD manifestations can take many forms. They range from asymptomatic elevation of transaminases to cirrhosis and end-stage liver disease. CFLD is diagnosed after excluding other causes of chronic liver disease. To date, there is no effective therapy to prevent or treat CFLD. Management of CFLD emphasizes on optimizing nutritional status. Ursodeoxycholic acid is the only available treatment that may prevent progression of CFLD at present. All CF patients with CFLD need annual investigations and follow-up for early detection of the disease. Liver transplantation should be considered in patients with decompensated cirrhosis and portal hypertension, with acceptable long-term outcomes. Novel therapies of CFLD are promising. This review article aims to summarize the published literature on CFLD, its pathophysiology, clinical features and complications, and management including new therapeutic options.

Wolcott-Rallison syndrome (WRS) is an autosomal recessive disease, characterized by neonatal or early-onset non-autoimmune insulin-dependent diabetes. WRS, although rare, is recognized to be the most frequent cause of neonatal-onset diabetes. The majority of reported patients are from consanguineous families. Several mutations with variable expression of the syndrome are reported. Here we describe a six-year-old boy with WRS who was evaluated at Sultan Qaboos University Hospital and was found to have a novel homozygous nonsense mutation in the EIF2AK3 gene. His younger sister also had WRS but with milder expression. The mutation exhibited different clinical characteristics in the siblings proving that WRS patients phenotypic variability correlates poorly to genotype. This is the first case report of two Omani children with WRS and a report of a novel mutation.