Clinical Information

Peroxisomes are organelles present in all human cells except mature erythrocytes. They carry out essential metabolic functions, including beta-oxidation of very long-chain fatty acids (VLCFA), alpha-oxidation of phytanic acid, and biosynthesis of plasmalogen and bile acids. Peroxisomal disorders include disorders of peroxisomal biogenesis with defective assembly of the entire organelle, and single peroxisomal enzyme/transporter defects where the organelle is intact but a specific function is disrupted. Peroxisomal beta-oxidation of VLCFA is impaired in all disorders of peroxisomal biogenesis and in selected single enzyme deficiencies, particularly X-linked adrenoleukodystrophy (X-ALD), resulting in elevated concentrations of VLCFA in plasma or serum.

Peroxisomal biogenesis disorders (PBD) include Zellweger syndrome spectrum disorders, which are clinically diverse and range in severity from neonatal lethal (Zellweger syndrome) to more variable clinical courses in neonatal adrenoleukodystrophy and infantile Refsum disease. Affected children typically have hypotonia, poor feeding, distinctive facial features, seizures, and liver dysfunction. Other features can include retinal dystrophy, hearing loss, developmental delays, and bleeding episodes. Rhizomelic chondrodysplasia punctata is another PBD. It is characterized by rhizomelic shortening, chondrodysplasia punctata, cataracts, intellectual disability, and seizures, although it can have a milder phenotype with only cataracts and chondrodysplasia. The typical biochemical profile shows normal VLCFA and elevated phytanic acid.

X-ALD is a neurologic disorder affecting the white matter and adrenal cortex. It can present between ages 4 and 8 years as a childhood cerebral form with behavioral and cognitive changes, associated with neurologic decline. Other forms include an "Addison disease only" phenotype with adrenocortical insufficiency without initial neurologic abnormality and adrenomyeloneuropathy associated with later-onset progressive paraparesis. X-ALD is an X-linked condition that primarily affects male patients; however, some female patients who are carriers can develop later-onset neurologic manifestations. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel, a list of conditions that are nationally recommended for newborn screening by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children.

Refsum disease is a peroxisomal disorder characterized by anosmia, retinitis pigmentosa, neuropathy, deafness, ataxia, ichthyosis, and cardiac abnormalities. The classic biochemical profile of Refsum disease is an elevated plasma or serum phytanic acid level.

Biochemical abnormalities in peroxisomal disorders include accumulations of VLCFA, phytanic acid, and pristanic acid. The differential diagnosis of these disorders is based on recognition of clinical phenotypes combined with a series of biochemical tests to assess peroxisomal function and structure. These include measurements and ratios of VLCFA, pipecolic acid (PIPA / Pipecolic Acid, Serum; PIPU / Pipecolic Acid, Random, Urine), phytanic acid and its metabolite pristanic acid. In addition, confirmatory testing for X-ALD (XALDZ / X-Linked Adrenoleukodystrophy, Full Gene Analysis, Varies) via molecular genetic analysis is available.