Prenatal and post-natal imaging of Zellweger spectrum disorder with novel prenatal sonographic findings

Peroxisomes are membrane-enclosed organelles in the cell which contain enzymes involved in various metabolic processes. Peroxisomal disorders are classified as peroxisome biogenesis disorder and single enzymatic defects. Zellweger spectrum disorder is an autosomal recessive condition affecting any of the 13 PEX genes responsible for synthesis and functioning of the peroxisomes. Prenatal diagnosis of Zellweger spectrum disorder has been possible in the recent years due to clinical exome sequencing of the amniotic fluid or chorionic villous sampling in suspected cases. The common prenatal imaging findings are Fetal akinesia/bradykinesia, Ventriculomegaly and echogenic kidneys. We present a case of antenatally suspected Zellweger syndrome, its post-natal imaging with confirmation of diagnosis by biochemical studies and clinical course. A 36-year-old multigravida, known case of SLE, was referred to us for a detailed anomaly scan at 25 weeks of gestation in view of fetal ventriculomegaly. Additional prenatal imaging findings were fetal hypokinesia, rhizomelia, persistent left SVC, echogenic kidneys, hepatomegaly with calcification, polyhydramnios and intrauterine growth restriction. Postnatally, neonate had dysmorphic facial features of high forehead, shallow supraorbital ridges, low-set ears with absent antihelix, hypertelorism, depressed nasal bridge, upturned nasal tip, and absent eyelashes. The neonate had repetitive seizures and elevated transaminases. On abdominal ultrasound, hepatomegaly with hepatic calcification, bilateral echogenic kidneys with cysts within were noted. On neurosonogram, lateral ventriculomegaly with bilateral germinolytic cysts was noted. An infantogram showed irregular stippled calcification of the epiphyses of bilateral patella, calcaneum, femoral head and olecranon. MRI brain showed bilateral lateral ventriculomegaly, brachycephaly with bilateral frontal and peri-sylvian polymicrogyria. The plasma of the neonate showed elevated very long-chain fatty acids and low plasmalogens. These biochemical findings are suggestive of peroxisome biogenesis disorder/RCDP. Our case reconfirms the most common prenatal findings of Zellweger spectrum disorder. The novel prenatal finding in our case was the hypoechoic enlarged liver with parenchymal calcification, IUGR, late onset polyhydramnios, and persistent left SVC. The overall prognosis of this disease is dismal, hence early prenatal detection is of utmost importance.