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PEROXISOMES

• Peroxisome: General
  • Single-membrane organelle
  • Present in nearly all eukaryotic cells
• Peroxisome functions
  • H₂O₂ metabolism
  • Ether-Phospholipid biosynthesis
  • Bile acid; Cholesterol; Plasmalogen synthesis
  • β-Oxidation: Fatty acids (Long & Very long chain)
  • Very-long chain Fatty acid-CoA
    • Types: C26:0 & C24:0
    • Enzymes in pathway
      • Straight-chain acyl-CoA oxidase
      • D-bifunctional protein
      • Thiolases: 3-Ketoacyl-CoA thiolase; Sterol carrier protein X
  • Branched chain Fatty acid-CoA
    • Types
      • Pristanoyl-CoA
      • Bile acid intermediates: THCA; Dihydroxycholestanoic acid (DHCA)
    • Enzymes in pathway
      • Branched-chain acyl-CoA oxidase
      • D-bifunctional protein
      • Thiolase: Sterol carrier protein X
  • Other: Amino acid & Purine metabolism
• Peroxisome contents: > 60 enzymes
• Peroxisome disorders: Classification & Disorders
  • Single enzyme: Affects single metabolic pathway
    • Hyperoxaluria type I
    • Refsum syndromes (Peroxisome Biogenesis Disorders)
    • Adrenoleukodystrophy
      • X-linked (ALDP)
    • Rhizomelic chondrodysplasia punctata (RCDP) : DHAPAT
    • β-Oxidation disorders
      • α-Methylacyl-CoA racemase (AMACR) deficiency
        • Type II
        • Type III (dihydroxyacetone phosphate acyltransferase)
      • D-bifunctional protein (DBP)
      • Straight-chain acyl-CoA oxidase
    • Sterol carrier protein 2
      • Leukoencephalopathy with Dystonia & Motor neuropathy
  • Peroxisomal biosynthesis
    • General
      • Disorders affect all of the metabolic pathways of peroxisome
      • Disorders can result from mutations in any > 14 genes: PEX genes
      • Peroxins: Products of PEX genes
      • PEX gene function: Peroxisome biogenesis
    • Disorders
      • Neonatal adrenoleukodystrophy (NALD): PEX10
      • Zellweger syndrome: PEX10
      • Ataxia: PEX10
      • Infantile Refsum disease (IRD): PEX1
      • Rhizomelic chondrodysplasia punctata (RCDP), Type I : PEX7
      • Mulibray nanism: TRIM37
  • ALS: DAO
• Peroxisome: External link

• Epidemiology: 1 family
• Mutation: Homozygous; Frameshift; 1-nucleotide insertion, 545_546insA
• SCP2 protein
  • Facilitates transport of cholesterol to mitochondria for first step in steroidogenesis
  • Low levels in Zellweger syndrome
  • Mutation: Absent activity
• Clinical
  • Onset age: Teens
  • Extrapyramidal
    • Head tremor: Dystonic
    • Spasmodic torticollis
  • Motor
  • Reflexes
    • Tendon: Arms increased; Legs reduced
    • Plantar relex: Flexor
  • Sensation: ? Reduced vibration
  • Eye: Saccadic movements
  • Cerebellar: Asymmetric ataxia; Nystagmus
  • Hyposmia
  • Endocrine
    • Hypergonadotrophic hypogonadism
    • Azoospermia
  • Differential diagnosis: AMACR deficiency
• Laboratory
  • MRI
    • Leukoencephalopathy
    • Lesions in thalamus, pons & occipital cortex
  • CSF: Normal
  • Pristanic acid: Increased
  • NCV
    • Motor neuropathy: Axon loss; Conduction block in legs
    • Sensory: small amplitude SNAPs
  • Evoked potentials: Abnormal corticospinal tracts & posterior columns