Laboratory Diagnosis in Neurology, 1 Ed.

Peroxisomal Diseases


Peroxisomes are cell organelles of up to 1.5 μm in size; they are surrounded by a single membrane. Their name refers to hydrogen peroxide, which is produced in these organelles by oxidases and degraded by catalase. There are over 50 peroxisomal enzymes catalyzing the degradation of very long chain fatty acids, branched fatty acids (phytanic acid), or the amino acid lysine via a secondary pathway (intermediate product: pipecolic acid). These enzymes also catalyze the synthesis of bile acids and plasmalogens; the latter are ether phospholipids that are highly concentrated in myelin layers. Peroxisomes reproduce by division, which requires the synthesis of membrane lipids and specific membrane proteins as well as the import of matrix proteins.

Classification and Clinical Features

Peroxisomal disorders are divided into two groups (Wanders, 1999):

• The first group includes disturbances in peroxidase development with dysfunction of several peroxisomal metabolic pathways:

– Zellweger's syndrome manifests at birth with facial dysmorphism, muscular hypotonia, seizures, ocular peculiarities, and hepatopathy. Infants show abnormal psychomotor development and a failure to thrive; they usually die during the 1st year of life.


– A similar but slightly milder clinical picture is seen in neonatal adrenoleukodystrophy and infantile Refsum's disease.

– In rhizomelic chondrodysplasia, skeletal abnormalities are accompanied by psychomotor retardation and spasticity.

• The second group of disorders includes dysfunctions of specific peroxisomal metabolic pathways:

– Manifestations of X-linked adrenoleukodystrophy (ALD) differ from one another according to the involvement of brain, spinal cord, peripheral nerves, and adrenal cortex (van Geel et al., 1997). The most common form is infantile or juvenile cerebral ALD, which starts with behavioral disturbances and deterioration in school performance. These are followed by rapid deterioration of sensory and mental capacities with development of spasticity, epilepsy, and addisonian symptoms. Death occurs after a few years. In adult cerebral ALD, psychosis, dyskinesia, ataxia, spastic spinal paralysis, or even the clinical picture of progressive multiple sclerosis may predominate. This form, too, ends in decerebration. More common in adulthood, however, is the manifestation as adrenomyeloneuropathy, although about 40% of these patients show cerebral involvement as well. About 10% of affected individuals have only Addison's disease without neurological symptoms. While there are also asymptomatic male carriers, 20% of female carriers show neurological defects.

– Refsum's disease is characterized by retinitis pigmentosa, cerebellar ataxia, and polyneuropathy. The age at onset of the disease varies widely; it is usually in adolescence, but can also be in early childhood or during the 5th decade of life (Wanders et al., 2001).


Table 17.6 shows specific laboratory parameters that are abnormal in these diseases. Very long chain fatty acids, phytanic acid, pristanic acid, pipecolic acid, and bile acid metabolites are determined in the serum or plasma by chromatography or mass spectrometry; pipecolic acid is also determined in the urine. Plasmalogens are generally measured in erythrocyte membranes (EDTA-blood) using similar methods; measurement in the serum has recently become possible. Blood samples are shipped to the laboratory at room temperature. In ALD, the blood analysis includes adrenal cortex hormones; CSF analysis reveals increased protein levels (as it does in Refsum's disease). Molecular genetic tests are also possible.