TN 36 (09-20)

DI 23022.535 Zellweger Syndrome




ZS; Peroxisomal Biogenesis Disorder (PBD); Zellweger Spectrum Syndrome (ZSS); Cerebro-hepato-renal Syndrome; CHR; ZWS; Zellweger leukodystrophy; Cerebrohepatorenal syndrome; PBD-ZSD; PDB, ZSS; peroxisome biogenesis disorders, Zellweger Syndrome Spectrum; Zellweger Spectrum; ZSD


Zellweger syndrome (ZS) is a rare, hereditary disorder affecting infants and usually resulting in death. Mutations in the PEX1 gene cause ZS. ZS belongs to the Zellweger spectrum of peroxisome biogenesis disorders (PBD, ZSS) and is considered the most severe of the PBDs. Infants with this condition are significantly impaired and usually die during the first year of life, usually having made no developmental progress.


Diagnostic testing: Biochemical abnormalities that are found in the blood and/or urine should be confirmed in cultured fibro blasts. The tests are used to detect accumulation of very long chain fatty acids (VLCFA) levels. Bony stippling (chondrodysplasia punctata) may be present on radiological studies and this is suggestive of ZS in the proper clinical setting. MRI of the brain may identify hypomyelination, cortical gyral abnormalities, and germinolytic cysts that are highly suggestive of ZS. Molecular genetic testing for mutations in the PEX genes.

Physical findings: Some physical findings with this condition include:

  • Unusual problems in prenatal development; an enlarged liver (hepatomegaly);

  • High level of iron and copper in the blood;

  • Vision disturbances;

  • Poor muscle tone;

  • Difficulty sucking or swallowing;

  • Glaucoma;

  • Retinal degeneration;

  • Cataracts;

  • Corneal clouding;

  • Brushfield spots (gray or pale yellow spots that go around the sides of the iris);

  • Optic nerve hypoplasia;

  • Impaired hearing;

  • Characteristic facial appearance;

  • Seizures;

  • Inability to feed;

  • Liver cysts with hepatic (liver) dysfunction;

  • Chondrodysplasia punctata;

  • Normal to large head circumference;

  • Clubbed feet;

  • Thumb rotation; and

  • Stippled chondral calcification of the patella and acetabulum.

ICD-9: 277.86

ICD-10: E71.510


The prognosis for infants with ZS is poor. Most infants do not survive past the first 6 months, and usually death is the result of respiratory failure, gastrointestinal bleeding, or liver failure.


There is no cure for ZS, nor is there a standard course of treatment. Since the metabolic and neurological abnormalities that cause the symptoms of Zellweger syndrome are present during fetal development, treatments to correct these abnormalities after birth will be limited. Most treatments are symptomatic and supportive and may include gastrostomy to provide adequate calories, hearing aids, cataract removal in infancy, glasses, vitamin supplements, primary bile acid therapy, anti-epileptic drugs and possibly monitoring for hyperoaluria, monitoring for coagulation factors and tests of liver function. Avoidance of cow’s milk products is recommended to reduce exposure to phytanic acid.


Suggested MER for Evaluation:

  • Clinical examination that describes diagnostic features of the impairment;

  • If available in the MER, Plasma VLCFA abnormalities as outlined above or mutations in the PEX genes confirm a diagnosis of one of the PBDs;

  • If such testing is not available, then a complete review of the clinical history, course, and laboratory studies on which the diagnosis is suspected will be needed for review; and

  • To differentiate the three PBDs and to evaluate the severity of the specific case, a complete physical and neurological examination.

Suggested Listings for Evaluation:





110.08 A


* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

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DI 23022.535 - Zellweger Syndrome - 09/09/2020
Batch run: 07/21/2021