Zellweger spectrum diseases (MSZ) result from abnormalities in the functions of cellular structures called peroxisomes.

They are also called peroxisome biogenesis disorders or generalised peroxisomal disorders.

Within the cell, the peroxisome performs several important functions necessary for the proper functioning of various organs, such as the nervous system, liver, and adrenal glands.

The severity of diseases on the Zellweger spectrum can vary from relatively moderate to severe, following a continuum of at least three pathologies: Zellweger syndrome, the most severe form, neonatal adrenoleukodystrophy, and infantile Refsum disease, the lesser form. These different pathologies were originally named before their biochemical and molecular basis had been determined.

The diagnosis of Zellweger spectrum diseases can be made by biochemical blood and / or urine examinations and confirmed by culture of skin fibroblasts. Specific biochemical tests are as follows: in blood: very long chain fatty acids, phytanic acid and pristanic acid, bile acids, plasma pipecolic acid, and red blood cell plasma genes; in urine: pipecolic acid, bile acids, oxalate.

Mutations in twelve different PEX genes, encoding peroxins, proteins involved in the transport of peroxisome enzymes, have been identified in diseases of the Zellweger spectrum. PEX1 is the most common cause of Zellweger spectrum diseases, present in approximately 70% of people.

The clinical course of infantile Refsum’s disease is variable.

It can include delayed intellectual and motor development, hearing loss, visual impairment, liver dysfunction, and moderate craniofacial abnormalities. The disease may get attention initially because the child fails a hearing test and / or has vision problems. Liver dysfunction may be seen first in a child with bleeding episodes caused by a coagulation abnormality in relation to vitamin K. These children may also have adrenal insufficiency. The overall clinical course may be stable, but the disease is often slowly progressive, with deterioration of hearing, sight and ability to walk. Some subjects can develop leukodystrophy with the consequence of the loss of acquired skills. Other people may have mainly sensory deficits in adulthood or only ataxia (abnormal movements).

Since people with Zellweger spectrum diseases can reach adulthood, clinical manifestations of these conditions should be monitored and treated such as:

• diet and nutrition;
• hearing aids;
• vision correction;
• for the liver, supplementation with fat-soluble vitamins;
• for adrenal insufficiency, supplementation with cortisol.

Experimental treatments are being studied, such as the administration of bile acids (cholic acid), docosahexaenoic acid and a diet low in phytanic acid. So far, treatment for Zellweger’s spectrum diseases remains primarily symptomatic and supportive.