A cell can contain several hundred peroxisomes, which are round or oval bodies with diameters of about 0.5 micron, that contain proteins that function as enzymes in metabolic processes. By definition, a peroxisome must contain catalase, which is an enzyme that breaks down hydrogen peroxide.

Approximately 50 different biochemical reactions occur entirely or partially within a peroxisome. Some of the processes are anabolic, or constructive, resulting in the synthesis of essential biochemical compounds, including bile acids, cholesterol, plasmalogens, and docosahexanoic acid (DHA), which is a long chain fatty acid that is a component of complex lipids, including the membranes of the central nervous system. Other reactions are catabolic, or destructive, and lead to the destruction of some fatty acids, including very long chain fatty acids (VLCFAs, fatty acids with more than 22 carbon atoms in their chains), phytanic acid, pipecolic acid, and the prostoglandins. The peroxisome is involved in breaking down VLCFAs to lengths that the body can use or get rid of.

When VLCFAs accumulate due to abnormal functioning of the peroxisomes, they are disruptive to the structure and stability of certain cells, especially those associated with the central nervous system and the myelin sheath, which is the fatty covering of nerve fibers. The peroxisomal disorders that include effects on the growth of the myelin sheath are considered to be part of a group of genetic disorders referred to as leukodystrophies. While metachromatic leukodystrophy (MLD) usually has its onset in infants or juveniles, there have been reports of its onset in young adults.

There are many other metabolic deficiencies that can occur in those who have peroxisomal disorders, which result in other types of detrimental effects, and together result in the abnormalities associated with the peroxisomal disorders. Unfortunately, it is not known how these abnormalities, and combinations of abnormalities, cause the disabilities seen in those afflicted with the disease.

Peroxisomal disorders form a heterogeneous disease group, with different degrees of severity. Included in the group referred to as PBD are:

• Zellweger syndrome (ZS), which is usually fatal within the first year of life,
• neonatal adrenoleukodystrophy (NALD), which is usually fatal within the first 10 years,
• infantile Refsum disease (IRD), which is not as devastating as ZS and NALD, as the children with this disorder with time and patience can develop some degree of motor, cognitive, and communication skills, although death generally occurs during the second decade of life.
• rhizomelic chondrodysplasia punctata (RCDP), which in its most severe form is fatal within the first year or two of life. However, survival into the teens has been known to occur. It is characterized by shortening of the proximal limbs (i.e., the legs from knee to foot, and the arms from elbow to hand).
• Zellweger-like syndrome, which is fatal in infancy, and is known to be a defect of three particular enzymes.

The differences among these disorders are continuous, with overlap between abnormalities. The range of disease abnormalities may be a result of a corresponding range of peroxisome failure; that is, in severe cases of ZS, the failure is nearly complete, while in IRD, there is some degree of peroxisome activity.

In peroxisomal single-enzyme disorders, the peroxisome is intact and functioning, but there is a defect in only one enzymatic process, with only one corresponding biochemical abnormality. However, these disorders can be as severe as those in which peroxisomal activity is nearly or completely absent.

X-linked adrenoleukodystrophy (X-ALD) is the most common of the peroxisomal disorders, affecting about one in 20,000 males. It is estimated that there are about 1,400 people in the United States with the disorder. In X–ALD there is a deficiency in the enzyme that breaks down VLCFAs, which then accumulate in the myelin and adrenal glands. Onset of X-ALD-related neurological symptoms occurs at about five–12 years of age, with death occurring within one to 10 years after onset of symptoms. In addition to physical abnormalities seen in other types of peroxisomal disorders, common symptoms of X-ALD also include behavioral changes such as abnormal withdrawal or aggression, poor memory, dementia, and poor academic performance. Other symptoms are muscle weakness and difficulties with hearing, speech, and vision. As the disease progresses, muscle tone deteriorates, swallowing becomes difficult and the patient becomes comatose. Unless treated with a diet that includes Lorenzo's oil, the disease will result in paralysis, hearing loss, blindness, vegetative state, and death. There are also milder forms of X-ALD: an adult onset ALD that typically begins between the ages of 21 and 35, and a form that is occasionally seen in women who are carriers of the disorder. In addition to X-ALD, there are at least 10 other single-enzyme peroxisomal disorders, each with its own specific abnormalities.

Most peroxisomal disorders are inherited autosomal recessive diseases, with X-ALD as an exception. They occur in all countries, among all races and ethnic groups. They are extremely rare, with frequencies reported at one in 30,000 to one in 150,000, although these numbers are only estimates.

In general, developmental delay, mental retardation, and vision and hearing impairment are common in those who have these disorders. Acquisition of speech appears to be especially difficult, and because of the reduced communication abilities, autism is common in those who live longer. Peroxisomal disorder patients have decreased muscle tone (hypotonia), which in the most severe cases is generalized, while in less severe cases, is usually restricted to the neck and trunk muscles. Sometimes this lack of control is only noticeable by a curved back in the sitting position. Head control and independent sitting is delayed, with most patients unable to walk independently.

Failure to thrive is a common characteristic of patients with peroxisomal disorder, along with an enlarged liver, abnormalities in liver enzyme function, and loss of fats in stools (steatorrhea).

Peroxisomal disorders are also associated with facial abnormalities, including high forehead, frontal bossing (swelling), small face, low set ears, and slanted eyes. These characteristics may not be prominent in some children, and are especially difficult to identify in an infant.

Since hearing and vision deficiencies may be difficult to identify in infants, peroxisomal disorders are usually detected by observations of failure to thrive, hypotonia, mental retardation, widely open fontanel, abnormalities in liver enzymes, and an enlarged liver. If peroxisomal disorders are suspected, blood plasma assays for VLCFAs, phytanic acid, and pipecolic acid are conducted. Additional tests include plasmalogen biosynthesis potential.

For many of the peroxisomal disorders, there is no standard course of treatment, with supportive treatment strategies focusing on alleviation of complications and symptoms. In general, most treatments that are attempted are dietary, whereby attempts are made to artificially correct biochemical abnormalities associated with the disorders. Therapies include supplementation of the diet with antioxidant vitamins, or limitation of intake of fatty acids, especially VLCFAs.

Another area of dietary therapy that is being investigated is the supplementation of the diet with pure DHA, given as early in life as possible, in conjunction with a normal well-balanced diet. Some results have indicated that if given soon enough during development, DHA therapy may prevent some of the devastating consequences of peroxisomal disorders, including brain damage and the loss of vision.

Other treatment strategies include addition of important missing chemicals. For example, in disorders where there is faulty adrenal function, replacement adrenal hormone therapy is used.

Any dietary changes should be monitored biochemically to determine if the supplements are having their desired effects and are not causing additional adverse effects.

Bone marrow transplants may be used to treat X-ALD, and can be effective if done early in the course of the childhood form of the disease.

Physical and psychological therapies are important for all types of peroxisomal disorders.

Patients with peroxisomal disorders, and particularly X-ALD, have been treated with a mixture of glycerol trioleate-glycerol trieucate (4:1 by volume), prepared from olive and rapeseed oils, and referred to as Lorenzo's oil (developed by parents of a son, Lorenzo, who had X-ALD, whose story was documented in the 1992 movie, Lorenzo's Oil), to decrease the levels of VLCFA. Other diets that have been tried include dietary supplementation with plasmalogen precursors to increase plasmalogen levels and with cholic acid to normalize bile acids. However, there has been only limited success demonstrated with the use of these treatments. More research is needed to determine the long-term safety and effectiveness of these treatment strategies.

Peroxisomal disorders range from life-threatening to cases in which people may function with some degree of mental and motor retardation. As of 2001, there was not yet a cure. Enzyme replacement therapies, including enzyme infusion, transplantation, and gene therapy, may hold promise for future advances in the treatment of these disorders. Research is being conducted to increase scientific understanding of these disorders and to find ways to prevent, treat, and cure them.

Unfortunately not enough is yet known about these diseases to develop comprehensive strategies for prevention. Genetic counseling is recommended for known or suspected carriers. As genes are identified that result in the disorders, genetic testing is being developed to identify carriers, who then can manage their reproduction to avoid the possibility of children being born with these deficiencies. As the genetic bases for the disorders are defined, prenatal diagnosis and identification of carriers will be facilitated. For example, for X-ALD, diagnosis can be made from cultured skin fibroblasts or amniotic fluid cells. This allows prenatal diagnosis and carrier identification in 90% of those affected. More recently it has been shown that biochemical diagnosis can be performed through chorionic villi biopsy, a procedure performed very early in the first trimester of pregnancy.

Animal models of ZS and X-ADL have been developed and are providing researchers with methods to define pathogenic mechanisms and to evaluate new therapies.