Introduction
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive disorders which cause defects in the formation and secretion of bile components and bile acids [1]. Progressive Familial Intrahepatic Cholestasis consists of five different variant forms numbered 1 through 5 based on the gene involved [2]. Most of these disorders present in infancy and early childhood as signs of growth failure vitamin K deficiency (i.e., easy bruising, epistaxis, coagulopathies) due to impaired vitamin K absorption and progressive liver disease leading to cirrhosis before adulthood [1. 2].
Progressive Familial Intrahepatic Cholestasis type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene located on chromosome 7 [3]. This gene encodes multidrug resistance protein-3 (MDR3). This 12-domain transmembrane plasmalemmal translocator actively transports phosphatidylcholine from the inner to the outer canalicular membrane to neutralize bile salts and prevent injury to biliary epithelial and bile canaliculi [4].
The PFIC-3 patients are homozygous or compound heterozygous for ABCB4 pathogenic variants; however, monoallelic ABCB4 variants may also result in cholestatic liver disease [5]. Genetic testing confirms the diagnosis of PFIC syndromes for all types, and immunostaining can confirm the diagnosis of PFIC types 2 and 3 [6. 7].
There were no approved pharmacological treatment options to treat PFIC that may lead to symptom relief or even limit the disease progression. Ultimately, liver failure would be the definitive result and may indicate a need for liver transplantation [6].
Case report
A 6 years old girl presented to the internal medicine clinic in King Saud medical city due to yellow discoloration of the sclera and skin and abdominal distension. The parents reported that their child has recently complained of tiredness, mild abdominal pain, itching, frequent bleeding, and epistaxis. Her parents have noticed the abdominal distension earlier. However, they have not sought any medical consultation until they noticed the yellow discoloration of the skin and mucous membranes at four. She was diagnosed with hepatic cirrhosis of unknown etiology at the time. Her family history was unremarkable, but the parents have mentioned that they were second-degree relatives.
The physical examination revealed a yellow discoloration of the skin sclera and the mucous membranes, failure to thrive, hepatosplenomegaly, moderate ascites, and ecchymosis in both legs.
Her vital signs were normal, and the physical examination was otherwise normal.
The abdominal ultrasonography examination reported that the liver was of average size measuring 11.5 cm coarse parenchymal echo pattern, with multiple small variable sizes ill-defined hypoechoic lesions (Fig. 1), the gallbladder had a thick wall yet no stones or biliary sludge were seen inside (Fig. 2), and splenomegaly was also reported. The examination was otherwise normal. The complete blood count test revealed mild normocytic normochromic anemia, mild leukopenia, and neutropenia, Thrombocytopenia, as hemoglobin levels were 11.2 g/dl (normal g/dl), hematocrit of 32.0 percent (normal percent), mean corpuscular volume of white blood cell count 4.47 10^3/ul (normal 10^3/ul), platelet count of 92 10^3/ul. Other laboratory tests revealed elevated serum AST of 223 U/L (normal < 40 U/L), ALT of 115 U/L (normal < 50 U/L), and total bilirubin levels of 4.14 mg/dl (normal 0.2-1.3 mg/dl), alkaline phosphatase levels of 647 U/L (normal 38 - 126 U/L) whereas serum GGT was not measured. Thyroid-stimulating hormone was also measured and revealed a serum level of 6.54 mIU/l (normal 0.465-4.68 mIU/L), the measurement of endomysial autoantibodies was positive. Other laboratory tests were in the normal range. The diagnosis of PFIC-3 was confirmed via detecting pathogenic variants in the ABCB4 gene. The patient has been listed as a candidate for liver transplantation, as the patient showed signs of portal hypertension in ultrasonography examination after a one-year follow-up.