IllnessPeroxisome biogenesis disorders, Zellweger spectrum; differential diagnosis

NGS +

Peroxisome biogenesis requires the coordinated activity of at least 16 PEX proteins encoded by PEX genes. Partial or generalized defects lead to two disease groups, Zellweger spectrum disorders (ZSD) and rhizomelic chondrodysplasia punctata type 1. Among ZSD, severe, intermediate, and milder forms occur, such as Zellweger syndrome (ZS; cerebro-hepato-renal syndrome), neonatal adrenoleukodystrophy and infantile Refsum disease. Furthermore, variant phenotypes exist for both groups. ZS patients develop hypotonia, feeding problems, hearing/vision loss, and epilepsy as neonates due to leukodystrophy. Affected individuals have characteristic facial features and usually do not survive past the first year of life. Patients with neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease have more variable symptoms and develop the disease late in infancy or early childhood. Here, the disease also typically progresses more slowly. NALD patients survive into childhood, and patients with infantile Refsum disease may reach adulthood. Rare cases show only developmental delays in childhood and hearing loss or vision problems beginning in adulthood without more severe features. Virtually all peroxisome biogenesis disorder are inherited in an autosomal recessive manner, only two of these disorders are autosomal dominant and one is X-linked. Summary studies of diagnostic yield are not available due in part to the immense spectrum of this cerebro-hepato-renal syndrome and variants. Inconspicuous genetic findings do not imply a definite exclusion of the suspected clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1448/https://www.ncbi.nlm.nih.gov/books/NBK1353/

https://www.ncbi.nlm.nih.gov/books/NBK1270/

https://www.ncbi.nlm.nih.gov/books/NBK1283/

https://www.ncbi.nlm.nih.gov/books/NBK1315/

• Alias: Infantile Refsum disease
• Alias: Neonatal adrenoleukodystrophy
• Alias: Peroxisomal biogenesis disturbances
• Alias: Peroxisome biogenesis disorder spectrum
• Alias: Zellweger spectrum disorder
• Allelic: Mitchell syndrome (ACOX1)
• Allelic: Optic atrophy 5 (DNM1L)
• Allelic: Perrault syndrome 1 (HSD17B4)
• Allelic: Rhizomelic chondrodysplasia punctata, type 1 (PEX7)
• Allelic: Rhizomelic chondrodysplasia punctata, type 5 (PEX5)
• Adrenoleukodystrophy (ABCD1)
• Adrenomyeloneuropathy, adult (ABCD1)
• D-bifunctional protein deficiency (HSD17B4)
• Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (DNM1L)
• Heimler syndrome 1 [Peroxisome biogenesis disorder 1C] (PEX1)
• Heimler syndrome 2 [Peroxisome biogenesis disorder 4C] (PEX6)
• Krabbe disease (GALC)
• Leukoencephalopathy with dystonia and motor neuropathy (SCP2)
• Metachromatic leukodystrophy (ARSA)
• Peroxisomal acyl-CoA oxidase deficiency (ACOX1)
• Peroxisome biogenesis disorder 10A [Zellweger] (PEX3)
• Peroxisome biogenesis disorder 10B (PEX3)
• Peroxisome biogenesis disorder 11A [Zellweger] (PEX13)
• Peroxisome biogenesis disorder 11B (PEX13)
• Peroxisome biogenesis disorder 12A [Zellweger] (PEX19)
• Peroxisome biogenesis disorder 13A [Zellweger] (PEX14)
• Peroxisome biogenesis disorder 14B (PEX11B)
• Peroxisome biogenesis disorder 1A [Zellweger] (PEX1)
• Peroxisome biogenesis disorder 1B [NALD/IRD] (PEX1)
• Peroxisome biogenesis disorder 2A [Zellweger] (PEX5)
• Peroxisome biogenesis disorder 2B (PEX5)
• Peroxisome biogenesis disorder 3A [Zellweger] (PEX12)
• Peroxisome biogenesis disorder 3B (PEX12)
• Peroxisome biogenesis disorder 4A [Zellweger] (PEX6)
• Peroxisome biogenesis disorder 4B (PEX6)
• Peroxisome biogenesis disorder 5A [Zellweger] (PEX2)
• Peroxisome biogenesis disorder 5B (PEX2)
• Peroxisome biogenesis disorder 6A [Zellweger] (PEX10)
• Peroxisome biogenesis disorder 6B (PEX10)
• Peroxisome biogenesis disorder 7A [Zellweger] (PEX26)
• Peroxisome biogenesis disorder 7B (PEX26)
• Peroxisome biogenesis disorder 8A [Zellweger] (PEX16)
• Peroxisome biogenesis disorder 8B (PEX16)
• Peroxisome biogenesis disorder 9B (PEX7)
• Refsum disease (PHYH)
• Retinal dystrophy with leukodystrophy (ACBD5)