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Sofia Sousa Nunes1, Ana Isabel Dias2, Marta Zegre Amorim1, Ana Cristina Ferreira3

1- Genetic Service, Pediatric Department, Centro Hospitalar Universitário de Lisboa Central, EPE
2- Neuropediatrics Service, Pediatric Department, Centro Hospitalar Universitário de Lisboa Central, EPE
3- Reference Center of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, EPE

- Poster em 16º Simposio Internacional da Sociedade Portuguesa de Doenças Metabólicas, Virtual, 11-13 novembro de 2020

Background: Zellweger spectrum disorder (ZSD) is a group of rare autosomal recessive disorders caused by mutations in more than 12 genes, that encodes a group of proteins essential for the formation and normal function of the peroxisomes. Mutations in the PEX1 gene are found in nearly 70% of affected individuals. The ZSD phenotypic spectrum is broad, ranging from mild manifestations to the most severe form, characterized by a distinctive facial appearance, visual and hearing impairment, hypotonia, developmental delay, seizures, hepatic dysfunction, renal cysts and bone abnormalities.
Case Report: Here we report a case of a 9-month-old male referred to our clinic by developmental delay, dysmorphic facial features and visual deficit.
The proband is the first child of a non-consanguineous couple from Cape Verde, born after 39 weeks gestation by eutocic delivery with adequate somatometry. He had seizures on the first months of life.
At clinical observation he had distinctive facies (epicanthus, flattened face, broad nasal bridge, high forehead, low-seat ears), large anterior fontanel with wide sutures, convergent strabismus with nystagmus movements, global hypotonia with lower limb spasticity and hepatosplenomegaly.
Diagnostic investigation showed increased transaminases with otherwise normal liver function; normal echocardiogram, renal ultrasound and skeleton X-ray. Ophthalmologic evaluation showed persistent hyperplastic primary vitreous. EEG demonstrated slow anomaly with moderate epileptiform activity over the left posterior temporal region. Brain MRI evidenced bilateral temporal polar sequel injuries of hemorrhagic vascular nature.
Metabolic investigation revealed elevated hexacosanoic acid on very long chain fatty acids study and peroxisomal dysfunction profile on urinary organic acids.
Leukodystrophy and leukoencephalopathy Next Generation Sequencing (NGS) panel identified 2 pathogenic variants in PEX1 gene, confirming the diagnosis of Zellweger spectrum disorder.
He started on early intervention program. Family genetic study is ongoing.
Comments: We emphasize the importance of NGS sequencing in the diagnosis of rare diseases as well as the importance of a multidisciplinary approach.