Zellweger syndrome

Also known as cerebrohepatorenal syndrome, it is a disorder that produces a decrease in the amount of peroxisomes in the cells. It is usually caused by alterations in one of the 13 PEX genes.

Zellweger syndrome is the most severe variant of peroxisome biogenesis disorders. It is characterized by neural defects, dysmorphic craniofacial features, neonatal seizures and liver dysfunction. It is genetic in origin and is inherited in an autosomal recessive pattern.

It is a genetic disorder.

This syndrome is caused by mutations in one of the 13 PEX genes encoding peroxin proteins. Pathogenic variants in the PEX genes can lead to alterations in peroxisome formation and peroxisomal dysfunction that can be more or less pronounced depending on the effect of the mutations.

Peroxisomes are cellular organelles essential for lipid metabolism (involved in the β-oxidation of very long-chain fatty acids), but they are also involved in the synthesis of plasmalogy;synthesis of plasmalogens (phospholipids abundant in brain and heart), bile acid production and glyoxylate detoxification.   


The incidence of Zellweger's syndrome in the general population is 1 case per 50,000 individuals and is highest in the Saguenay-Lac St Jean region of Quebec (Canada), with about 1 case per 12,000 inhabitants.


The first symptoms appear in the neonatal period, organ malformation and peroxisomal dysfunction occur. Newborns present with characteristic craniofacial abnormalities and macrocephaly or microcephaly. Skeletal anomalies and the presence of subcortical renal cysts are frequent. There is often growth retardation, hepatomegaly, jaundice and coagulopathy. Ocular disturbances, progressive visual loss and sensorineural hearing loss may occur. Central nervous system function is severely affected and patients suffer profound psychomotor retardation. Severe hypotonia, neonatal seizures, hepatic dysfunction or leukodystrophy occur.

Cases have been described of patients with symptoms that may be severe, intermediate or mild that correlate with the degree of peroxisomal activity involvement. Complete peroxisome loss results in a lethal developmental disorder, Zellweger's syndrome, while milder dysfunction can cause vision and hearing loss, nail and enamel abnormalities, and various neurological defects.

Disease management

The focus is on symptomatic treatment and may include gastrostomy to provide nourishment. Vitamin, folic acid and DHA supplements are used. Use of hearing aids to treat hearing loss; surgery to intervene for cataracts and glaucoma, if present, and use of glasses for vision problems.

 Anticonvulsant medication and early intervention services are used for developmental delay and intellectual disability; adrenal replacement therapy and supportive treatment for oxalate kidney stones and surgical intervention.

Genes analyzed



Bose M, Yergeau C, D'Souza Y, Cet al. Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review. Cells. 2022 Jun 10;11(12):1891.

Braverman NE, Raymond GV, Rizzo WB, et al. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-21.


Steinberg SJ, Raymond GV, Braverman NE, et al. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

GeneReviews® [Internet].

Wangler MF, Hubert L, Donti TR, et al. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283.

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