Successful Treatment of Severe Hepatopulmonary Syndrome as a Rare Complication of Zellweger Spectrum Disorder

Abstract

We report the case of an 11-year-old girl who developed hepatopulmonary syndrome (HPS) as a rare complication of Zellweger spectrum disorder and was successfully treated with liver transplantation. Our patient presented with neonatal sensorineural hearing loss. Muscular hypotonia, global developmental delay, and pigmentary retinopathy in infancy led to a diagnosis of peroxisomal biogenesis disorder due to compound heterozygous PEX1 variants. Despite feeding disorder, poor weight gain, mild liver disease with subclinical coagulopathy, she had a relatively uneventful course, attaining developmental milestones till 7 years of age, when she was noted to have persistent central cyanosis (TcSO₂ 72%) with poor oxygen response. Echocardiogram and CT chest were normal. Liver ultrasound demonstrated mild portal hypertension with a small spleen. An ultrasound bubble test established extracardiac right-left shunting, and perfusion scintigraphy confirmed the diagnosis of HPS. Angiography showed increased portal pressure with normal right atrial pressures, ruling out porto-pulmonary hypertension. Due to the limited prognosis of HPS and inadequate oxygenation on 2 L/min oxygen supplementation, after multidisciplinary discussion, a decision was made to proceed with an orthotopic liver transplant (OLT). Seven months later, she underwent OLT, following which her saturation normalized. At age 11 years, she continues to be clinically stable without oxygen supplementation. HPS being a rare complication of liver disease, is not easily recognized in the pediatric population. OLT proved beneficial in this child with an intermediately severe disorder of peroxisomal biogenesis.