Discussion
PFIC-3 is an autosomal recessive disease. This is a rare case of PFIC-3, which results from consanguineous parents. The parents are second-degree relatives with no clinical signs of PFIC-3. Neither the mother nor the patient had reported jaundice in the post gestation period. The patient’s siblings are unaffected but were recommended for carrier testing.
PFIC-3 usually manifests in later childhood or young adulthood. Unlike type 1 and type 2, PFIC-3 has a later onset and slower prognosis [8]. In our case, signs of splenomegaly appeared in the infancy period, but jaundice was delayed until four years of age. Occasional ascites and leg pigmentations have been noted after. Coagulation profile abnormalities are coherent with obstructive chronic liver disease. Infections with Salmonella typhi or Brucella were excluded. Serology testing for Hepatitis B and C were also negative.
A variant of uncertain significance has been detected in the PC gene, which is associated with pyruvate carboxylate deficiency. Although the clinical picture is not adequately consistent with severe types of pyruvate carboxylate deficiency, episodic types cannot be excluded. Thus, further genetic counseling may be required.
Symptomatic treatment involving Ursodeoxycholic acid was ordered. The patient is beginning to show signs of portal hypertension. She is on the list for liver transplantation, and it’s expected to be fully curable.
A similar case has been described by Zhang et al. [9] in which PFIC-3 is combined with biliary atresia. A 4-month-old female presented with severe jaundice, pruritus, and pale stool for 20 days. Abnormally strong echoes near the portal area, an abnormally small gallbladder with an irregularly stiff wall, and splenomegaly were identified on abdominal ultrasound. Blood tests showed elevated liver enzymes as well. Kasai portoenterostomy was enough to relieve clinical symptoms and improve blood tests. To compare with our Case, this patient presented at a younger age, with more complicated symptoms due to biliary atresia, and eventually required the Kasai procedure. Similar ultrasound features and elevated liver blood tests were observed. The diagnosis was confirmed by genetic testing of the ABCB4 gene as well.
Additionally, Lipiński et al. have reported four cases of PFIC-3 [10]. The mean age was 7. Only two of them presented with pruritus, and all of them had splenomegaly. All of them established chronic cholestatic liver disease of unknown etiology, which was the key to order genetic counseling. Several novel variants have been identified. They concluded that the clinical phenotype of PFIC-3 could be variable, and the diagnosis of PFIC-3 is difficult because some PFIC-3 patients initially presented with no jaundice. Fortunately, in our case, our patient’s main complaint was jaundice, which helped faster diagnosis.
Conclusion :
Children with jaundice, and elevated liver enzymes, with unknown etiology, should always be considered for genetic testing. Although PFIC-3 is not widely common, we recommend that consanguineous parents should undergo genetic counseling before conceiving.