Peroxisomal disorders


Peroxisomal disorders are a group of congenital diseases characterized by the absence of normal peroxisomes in the cells of the body.


Peroxisomes are organelles within a cell that contain enzymes responsible for critical cellular processes. A cell can contain several hundred peroxisomes, 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.

Peroxisomal disorders are subdivided into two major categories: those disorders resulting from a failure to form intact, normal peroxisomes, resulting in multiple metabolical abnormalities, which are referred to as peroxisome biogenesis disorders (PBD) or generalized peroxisomal disorders; and those disorders resulting from the deficiency of a single peroxisomal enzyme. There are about 25 known peroxisomal disorders, although the number of diseases that are considered to be separate, distinct peroxisomal disorders varies among researchers and healthcare practitioners.

Approximately 50 different biochemical reactions occur entirely or partially within a peroxisome. Some of the processes are anabolic (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 (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.

Peroxisomal disorders form a heterogeneous disease group, with different degrees of severity. The differences among these disorders are continuous, with overlap between abnormalities. Examples of peroxisomal disorders are:

  • X-linked adrenoleukodystrophy (X-ALD), a sex-linked disorder characterized by progressive symptoms that begin as behavioral changes, muscle weakness, and speech difficulties.
  • Zellweger syndrome (ZS), which is usually fatal within the first year of life.
  • Neonatal adrenoleukodystrophy (NALD), which is usually fatal within the first ten 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 known to be a defect of three particular enzymes.


Most peroxisomal disorders are inherited autosomal recessive diseases. This means that both parents need to be carriers of the defective gene in order for a child to develop the disease. If both parents are carriers but do not show signs of disease, each child has a 25 percent chance of having the disease. If one parent has the disease and the other is a carrier, each child has a 50 percent chance of having the disease. As a sex-linked genetic disorder, the daughters of males affected with X-ALD become carriers and the sons are not affected. The children of female carriers have a 50 percent chance of having the genetic mutation, which means that sons who inherit the mutation have the disease, and daughters who inherit the mutation are carriers.


Peroxisomal disorders 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. 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. ZS is estimated to affect one in 50,000 to 100,000 live births.

Causes and symptoms

The range of disease abnormalities may be a result of a corresponding range of peroxisome failure. For example, 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. These disorders, however, can be as severe as those in which peroxisomal activity is nearly or completely absent.

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.

In X-ALD there is a deficiency in the enzyme that breaks down VLCFAs, which then accumulate in myelin and the adrenal glands. Onset of X-ALD-related neurological symptoms occurs at about five to 12 years of age, with death occurring within one to ten 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 a mixture of oils called 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 ten other single-enzyme peroxisomal disorders, each with its own specific abnormalities.

When to call the doctor

A healthcare provider should be contacted if a child develops symptoms suggestive of peroxisomal disorder or if a child already diagnosed with a peroxisomal disorder shows signs of worsening disease.


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.

It is possible to diagnose peroxisomal disorders in utero. 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 percent of those affected. As of the early 2000s it has been shown that biochemical diagnosis can be performed through chorionic villus testing, a procedure performed very early in the first trimester of pregnancy.


For many of the peroxisomal disorders, there is no standard course of treatment, with supportive treatment strategies focusing on alleviation of complications and symptoms. Bone marrow transplants may be effective for children with X-ALD if administered early in the course of the childhood form of the disease. Physical and psychological therapies are important for all types of peroxisomal disorders.

Alternative treatment

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 the 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 with varying success include dietary supplementation with plasmalogen precursors to increase plasmalogen levels and with cholic acid to normalize bile acids.

Nutritional concerns

In general, most treatments that are attempted for peroxisomal disorders 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 the loss of vision and brain damage.

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.


Peroxisomal disorders range from life-threatening to cases in which people may function with some degree of mental and motor delays. As of 2004, there was not yet a cure for peroxisomal disorders. Enzyme replacement therapies, including enzyme infusion, transplantation, and gene therapy, may hold promise for future advances in the treatment of these disorders. As of the early 2000s research is conducted in order to increase scientific understanding of these disorders and find ways to prevent, treat, and cure them.


It is not possible to prevent the transmission of an abnormal peroxisomal gene from parent to child or spontaneous mutations that may arise.

Parental concerns

Numerous professional and parent-led organizations exist to support parents as they first learn of a peroxisomal disorder diagnosis and as they provide care for their child. 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.


Adrenal glands —A pair of endocrine glands (glands that secrete hormones directly into the bloodstream) that are located on top of the kidneys. The outer tissue of the glands (cortex) produces several steroid hormones, while the inner tissue (medulla) produces the hormones epinephrine (adrenaline) and norepinephrine.

Autosomal recessive mutation —A pattern of genetic inheritance where two abnormal genes are needed to display the trait or disease.

Autosome —A chromosome not involved in sex determination.

Enzyme —A protein that catalyzes a biochemical reaction without changing its own structure or function.

Fontanelle —One of several "soft spots" on the skull where the developing bones of the skull have yet to fuse.

Organelle —A specialized structure within a cell, which is separated from the rest of the cell by a membrane composed of lipids and proteins, where chemical and metabolic functions take place.



Moser, Hugo W. "Disorders of Very Long Chain Fatty Acids: Peroxisomal Disorders." In Nelson Textbook of Pediatrics , 17th ed. Edited by Richard E Behrman et al. Philadelphia: Saunders, 2004.


Martinez, Manuela. "The Fundamental and Practice of Docosahexanoic Acid Therapy in Peroxisomal Disorders." Current Opinion in Clinical Nutrition and Metabolic Care 3 (2000): 101–8.

Martinez, M., et al. "Therapeutic Effects of Docosahexanoic Acid in Patients with Generalized Peroxisomal Disorders." American Journal of Clinical Nutrition 71 (2000): 376–85.

Moser, Hugo W. "Molecular Genetics of Peroxisomal Disorders." Frontiers in Bioscience 5 (March 1, 2001): 298–306.

Senior, Kathryn. "Lorenzo's Oil May Help to Prevent ALD Symptoms." The Lancet Neurology 1, no. 8 (December 2002): 468.


The Myelin Project. 2136 Gallows Rd., Suite E, Dunn Loring, VA 22027. Web site:

United Leukodystrophy Foundation. 2304 Highland Dr., Sycamore, IL 60178. Web site:


Chedrawi, Aziza, and Gary Clark. "Peroxisomal Disorders." eMedicine , April 28, 2002. Available online at (accessed January 16, 2005).

Judith Sims Stephanie Dionne Sherk

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