Overview

The Zellweger spectrum results from defective peroxisome activities, resulting in a variety of phenotypes.

Historically, 3 syndromes were described, listed from most- to least- severe:

• Zellweger syndrome (or cerebrohepatorenal syndrome)
• Neonatal adreno-leukodystrophy
• Infantile Refsum disease

These have now been recognised as phenotypes of varying severity with a shared peroxisomal basis, and are now referred to as peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD)

[Braverman et al, 2016]

Clinical features

The clinical presentation varies in severity, and involves multiple organ systems:

• Hypotonia
• Seizures
• Craniofacial abnormalities
• Eye abnormalities
• Neuronal migration defects
• Hepatomegaly
• Skeletal defects

The hypotonia in particular can range from moderate motor delay to little spontaneous movement at all.

Patients with the more severe phenotype usually die in the first year of life, while those with milder phenotypes survive into young adulthood.

[Steinberg et al, 2006]

Epidemiology

The incidence of of Zellweger spectrum disorders has been measured at 1:133,000 in the United States, and 1:500,000 in Japan.

[Steinberg et al, 1993]

Pathophysiology

Peroxisomes are membrane-bound organelles ubiquitous among eukaryotic cells. These organelles form through replication by fission from other peroxisomes, or can originate from the endoplasmic reticulum.

The peroxisome matrix hosts over 70 distinct enzymes required for normal lipid metabolism and other biochemical processes.

Defects in the function of these organelles therefore has wide-ranging impacts across all organ systems.

Impacts on anaesthesia

Adrenal insufficiency

Case reports Primary adrenal insufficiency has been described in Zellweger spectrum disorders, and patients are generally screened for this on a yearly basis. Steroid stress dosing should therefore be considered.

[Berendse et al, 2014]

Suxamethonium

Expert opinion As with any condition causing hypotonia, experience with other conditions raises the question of acetylcholine receptor upregulation with attendant hyperkalaemia and rhabdomyolysis risk on exposure to suxamethonium.

Avoiding suxamethonium is reasonable on this basis, though no data is available on Zellweger spectrum disorders in particular.

[Hovgaard et al, 2021]