Pseudo-Zellweger syndrome

Pseudo-Zellweger syndrome, also known as pseudo-neonatal adrenoleukodystrophy or 3-oxoacyl-CoA thiolase deficiency (peroxisomal thiolase deficiency), is an extremely rare peroxisomal disorder that clinically resembles Zellweger syndrome (cerebrohepatorenal syndrome) but is caused by a distinct biochemical defect. Specifically, it results from a deficiency of peroxisomal 3-oxoacyl-CoA thiolase (also called peroxisomal beta-ketothiolase), an enzyme involved in peroxisomal fatty acid beta-oxidation. Unlike classic Zellweger syndrome, in which peroxisomes are absent or severely reduced, patients with pseudo-Zellweger syndrome have structurally present peroxisomes but with impaired function of this specific enzyme. The condition presents in the neonatal period with features strikingly similar to Zellweger syndrome, including severe hypotonia, seizures, craniofacial dysmorphism, hepatomegaly with liver dysfunction, and profound developmental delay. Affected infants may also exhibit visual and hearing impairment, as well as elevated very long-chain fatty acids (VLCFAs) in plasma, reflecting the impaired peroxisomal beta-oxidation. The neurological involvement is severe, with progressive white matter disease and neuronal migration defects reported in some cases. Additional features may include renal cysts and skeletal abnormalities such as stippled epiphyses (chondrodysplasia punctata). The prognosis for pseudo-Zellweger syndrome is very poor, with most affected infants dying in early infancy or childhood. There is currently no curative treatment available. Management is supportive and symptomatic, focusing on seizure control, nutritional support, and management of organ-specific complications. Genetic counseling is recommended for affected families.

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