Non-syndromic perspective on a unique progressive familial intrahepatic cholestasis variant: ZFYVE19 mutation.

Background: ZFYVE19 mutation has been recently identified as one of the non-syndromic causes of cholestasis. It is associated with elevated gamma-glutamyl transferase levels and is likely a cause of neonatal-onset and intrahepatic cholestasis.

Case: Here, we report a rare case of ZFYVE19 defect, confirmed by whole exome sequencing (WES). Our patient, who is currently 4 years old, presented to us at the age of 2 years with elevated levels of serum transaminases and bilirubin. WES revealed a homozygous ZFYVE19 mutation despite preserved synthetic liver function. This gene has recently been identified in the literature as a cause of non-classical progressive familial intrahepatic cholestasis (OMIM # 619849). Treatment with an appropriate dose of ursodeoxycholic acid resulted in the regression of elevated liver enzymes and itching. The patient's body mass index progressively increased throughout the treatment period. No medication side effects were observed at any point. Currently, the patient remains asymptomatic during follow-up.

Conclusion: We have identified the ZFYVE19 mutation as a variant that is not accompanied by any other symptoms. However, we have limited knowledge about the progression of the disease and are closely monitoring the patient for potential liver-related issues. Using WES in cases of undiagnosed liver enzyme elevations or cholestasis can help identify new genes and improve our understanding of the underlying pathophysiology.