Peroxisomal Diseases

Key Features

• Dysmorphic features, hypotonia, hearing loss, seizures, cataracts, retinopathy, liver disease and renal disease are characteristic findings of severe peroxisomal disease.

• Change in behavior or school failure in a young boy may suggest X-linked adrenoleukodystrophy and warrants a brain MRI with contrast.

• Very-long-chain fatty acid analysis is a good screening test for most, but not all, peroxisomal disorders.

• In peroxisomal biogenesis disorders, multiple enzymes are deficient

• Except for adrenoleukodystrophy, all peroxisomal diseases are autosomal recessive and can be diagnosed in utero

Clinical Findings

• Patients present as neonates or infants with

  • Seizures

  • Hypotonia

  • Characteristic facies with a large forehead and fontanel

  • Cholestatic hepatopathy

  • Retinal dystrophy

  • Hearing loss

• At autopsy, renal cysts, brain neuronal migration abnormalities, and absent or empty peroxisomes are seen

• Patients with milder biochemical and clinical phenotype have ataxia, developmental delay, and hearing and vision loss

• In other peroxisomal diseases, only a single enzyme is deficient

• Primary hyperoxaluria (alanine-glyoxylate aminotransferase deficiency) causes renal stones and nephropathy

• Defective phytanic acid oxidation in adult Refsum disease causes ataxia, leukodystrophy, cardiomyopathy, neuropathy, and retinal dystrophy

• Other isolated enzyme deficiencies can mimic Zellweger syndrome

Diagnosis

• The best screening test for Zellweger syndrome spectrum is determination of very-long-chain fatty acids in plasma

• Urine bile acids are abnormal in other peroxisomal disorders

• Phytanic acid and plasmalogens can also be measured

• Fibroblast enzyme assays and molecular analysis provide confirmation

Treatment

• Bone marrow transplantation may be an effective treatment at the early stages of adrenoleukodystrophy, and close monitoring of affected males is necessary

• Adrenal insufficiency requires hydrocortisone substitution

• Dietary treatment is used and effective for adult Refsum disease

• Liver transplantation protects the kidneys in severe primary hyperoxaluria