Endocrine Abstracts

Introduction: Zellweger Spectrum Disorders, one of the two groups of Peroxisome Biogenesis Disorders (PBD-ZSD) are rare, complex autosomal recessive genetic anomalies characterised by mutations in any of the PEX genes which are responsible for defective peroxisomes activity. The peroxisomes are organelles that play a primary role mainly in the lipid metabolism of almost all the cells of the body, hence their defective biosynthesis, assembly or biochemical functions turn PBD-ZSD into a multi-organ disease. The disease progression is variable, with a wide spectrum of clinical phenotypes and may include the onset of adrenal insufficiency.

Case report: We report the case of a 2 year-old girl who was previously diagnosed with a malfunctioning PEX6 protein as a result of biallelic pathogenic variants in PEX6 gene. The medical history work-up draws attention to the overall developmental delay, psychomotor retardation, partial vision and hearing loss and seizures under treatment with antiepileptic drugs. Among the clinical features we emphasize the small size, craniofacial dysmorphism, dysphagia, poor feeding and hepatomegaly. Laboratory data revealed elevated liver functions, abnormal coagulation profile and modified adrenal tests: elevated adrenocorticotropic hormone (ACTH) with normal morning cortisol level. The diagnosis of subclinical adrenal insufficiency was confirmed by the impaired plasma cortisol response following the Synacthen test. Hydrocortisone supplementation was recommended during stressful situations and intercurrent illness.

Discussion: Our patient’s clinical picture fits with an intermediate PBD-ZSD. Given the complexity of the disease, the management of PBD-ZSD is multidisciplinary and it focuses mostly on symptomatic or supportive treatment. These patients need close monitoring for adrenal insufficiency onset, which may by life-threatening if the diagnosis is delayed. Experts recommend yearly endocrinological check-ups by measuring serum morning cortisol and ACTH. Also, the endocrinological management may include vitamin D supplementation and bisphoshonates treatment, as patients with PBD-ZSD are at risk for osteopenia over time.