Zellweger Spectrum Disorders
Zellweger spectrum of peroxisome biogenesis disorders comprises Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease. These three diseases have overlapping clinical phenotypes. Zellweger syndrome is considered to be the most severe form, NALD intermediate, and infantile Refsum disease the least severe.
Onset of manifestations is usually in the newborn period or later in childhood and includes hypotonia, seizures, distinctive craniofacial features (flattened facies, large anterior fontanelle, widely split sutures, and broad nasal bridge), feeding difficulties, and liver dysfunction. Older children experience sensorineural hearing loss, retinal dystrophy and developmental delays. Affected individuals may also have skeletal abnormalities, adrenal insufficiency, episodes of hemorrhage and intracranial bleeding, and coagulopathy.
The Zellweger spectrum disorders are inherited in an autosomal recessive manner. The Zellweger spectrum disorders are estimated to occur in 1 in 50,000 individuals.
Indications for genetic testing:
- Confirmation of clinical diagnosis
- Carrier status detection of known mutation
- Prenatal diagnosis for known familial mutation
- Genetic counseling
Gould SJ et al. The peroxisome biogenesis disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8 ed. New York, NY: McGraw-Hill; 2001:3181-218.
Krause C et al. Identification of novel mutations in PEX2,PEX6,PEX10,PEX12, and PEX13 in Zellweger spectrum patients. 2006. Human Mutation 27 (11): 1157.
Steinberg SJ et al. Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum. GeneReviews® 2003 Dec 12 (Updated 2012 May 10)