Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Abstract

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

“…As discussed later, mitochondrial diseases can present with retinal dysfunction. Similarly, peroxisomal disorders such as Zellweger syndrome, adrenoleukodystrophy and Refsum’s disease cause severe retinal degeneration (Braverman et al, 2016), suggesting that both organelles are vital for retinal function.…”

Diagnosis of a mild peroxisomal phenotype with next-generation sequencing

“…Early diagnosis would allow for close surveillance of systems affected by PBD-ZSS [15], [29]. Our patient's C26:0-lyso-PC level on blood spot at eight years of age was outside of normal range and may have prompted further testing if this result was obtained on a neonatal screen.…”

“…Typically, the primary step in making PBD-ZSS diagnosis is measuring serum VLCFA [29]. However, the first diagnostic step of this case was sequencing.…”

Genetic Interactions between PEROXIN12 and Other Peroxisome-Associated Ubiquitination Components

“…Affected patients display developmental delays and neurological defects, and there is no cure (Braverman et al, 2016). PEX12, PEX2, and PEX10 mutations are found in approximately 4% to 9%, 15% to 4%, and 3% to 5% of peroxisome biogenesis disorder patients, respectively (Steinberg et al, Figure 9.…”