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Zellweger Syndrome Spectrum (ZSS)

There are three disorders considered to be part of the Zellweger spectrum: Zellweger Syndrome (ZS), Neonatal Adrenoluekodystrophy (NALD), and Infantile Refsum Disease (IRD).  Each of these three disorders have a similar cause and reflect varying degrees of severity, with ZS being the most severe and IRD the least severe.

Diagnosis/testing

The measurement of plasma very-long-chain fatty acid (VLCFA) concentrations is the most commonly used and most informative initial screen.  High levels of plasma C26:0 and C26:1 and the ratios of C24/C22 and C26/C22 indicates a problem with breaking down peroxisomal fatty acids.  The degree of VLCFA plasma concentration elevation may vary, with a small percentage of indviduals demonstrating only modest elevations.

Molecular genetic testing can be done to determine which gene contains the defect.  Defects in twelve different PEX genes have been identified in ZSS.

Treatment

There is no cure for any of the disorders of the Zellweger spectrum.  Treatment is usually symptomatic and supportive. 

Feeding tubes are usually required to provide adequate calories, hearing aids can be used for those showing hearing impairment, cataract removal to preserve vision (if present).  Supplementation of vitamin K and other fat-soluble vitamins are recommended.  Primary bile acid therapy may improve liver function.  Standard anti-epileptic drugs may be used in an attempt to control seizures.  Suction may be needed for those who cannot manage their saliva. 

The use of docosahexaenoic acid (DHA) has been suggested. This compound is important in brain and retinal function and is low in children with ZSS. The use of DHA supplementation in these individuals is presently undergoing evaluation.  Please visit the Martinez Foundation site for more information about the use of DHA.

Inheritance

The disorders of the Zellweger Syndrome spectrum are inherited in an autosomal recessive manner.  It  affects all races, male and female.  The children of two carriers have a 1 in 4 (25%) chance of being affected, a 50% chance of being another unaffected carrier, and a 25% chance of being unaffected and not a carrier. 

Clarification of carrier status and the availability of prenatal testing can be discussed with a genetic counsler before another pregnancy.

Zellweger Syndrome ZS (Cerebro-Hepato-Renal Syndrome)

Clinical Features

Zellweger syndrome is characterized by presentation in the neonatal period with profound hypotonia, characteristic facies, large fontanelle (soft spots), seizures, inability to feed, liver cysts with hepatic dysfunction, and chondrodysplasia punctata.  Infants with this condition are significantly impaired and usually die during the first year of life, usually having made no developmental progress.  Death is usually secondary to progressive apnea or respiratory compromise from infection.

Neonatal Adrenoluekodystrophy NALD and Infantile Refsum Disease IRD

NALD and IRD may present in the neonatal period, but generally surface later as a result of hearing loss, retinal dystrophy, developmental delay with hypotonia and liver dysfunction.  The clinical course is variable.  The condition is often slowly progressive and hearing and vision worsen with time.  Some individuals may lose previously acquired skills due to myelin degeneration (leukodystrophy).  Children who survive the first year and who have a non-progressive course have a 77% probability of reaching school age.

Seizures are usually absent in IRD but not in NALD, which involves exclusive atrophy of the adrenal cortex.  Likewise renal cysts and chondrodysplasia punctata are not typically present.        

Rhizomelic chondrodysplasia punctata I

RCDP Type I is a multi-enzyme peroxisomal disorder with a very similar appearance to Zellweger syndrome, yet is clinically distinct from the Zellweger syndrome spectrum.  Various forms of inheritance have been described (autosomal, x-linked, dominent, recessive).

In children with RCDP Type I, Plasmalogen deficiencies are consistant and useful in diagnosis.

Information taken from the National Institute of Health's GeneReview site and an article by Aziza K Chedrawi, MD, Texas Children's Hospital.

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Last updated: June 1, 2007