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.