Zellweger spectrum disorders: clinical overview and management approach

Abstract

Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focuses on the management of patients with a ZSD and provides recommendations for supportive therapeutic options for all those involved in the care for ZSD patients.

Clinical Diagnosis, Biochemical Findings, Genetics and Incidence of Zellweger Syndrome

“…The liver disease of ZS is typical, manifesting as hepatomegaly, conjugated hyperbilirubinemia, and abnormal liver function test results (5). In some patients, liver disease can progress to splenomegaly, cirrhosis, and portal hypertension (15).…”

“…Infants with ZS typically present in the neonatal period with profound muscular hypotonia, poor feeding behavior, frequent seizures, jaundice, hepatic dysfunction, bone abnormalities, and specific craniofacial dysmorphism (4,5). The infants have poor prognoses and usually die within the first year of life (4,6).…”

“…Consequently, mutations in PEX genes cause deficiencies in peroxisome numbers or function, or mosaic patterns (5,6,8). Peroxisomes are present in all cells except mature erythrocytes and are particularly common in renal and hepatic cells (9,10).…”

“…Although the incidence of ZS differs by region, the overall incidence is estimated to be 1 in 50,000 -100,000 births (5,14). We reviewed seven patients diagnosed with ZS in four centers in Diyarbakir, Turkey, over the past 4 years and estimated the incidence of ZS.…”

Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders

“…β-oxidation of very long-chain fatty acids (VLCFA), α-oxidation of phytanic acid, bile acid synthesis, and plasmalogen biosynthesis) a defect in peroxisome biogenesis leads to multiple metabolic abnormalities in these patients (Wanders and Waterham 2006). Patients can present with a variety of symptoms and the severity ranges from death in infancy to adults with an isolated vision and hearing deficit (Klouwer et al 2015). With an estimated incidence of 1:50.000 (Gould et al 2001) ZSDs are considered rare, however, an increasing number of patients with a relatively mild phenotype have been identified in recent years (Régal et al 2010;Ebberink et al 2010;Sevin et al 2011;Mignarri et al 2012;Ebberink et al 2012;Ratbi et al 2015;Renaud et al 2016;Ventura et al 2016).…”