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Peroxisomal Disorders


Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Peroxisomal disorders are a group of hereditary metabolic disorders that occur when peroxisomes are missing or do not function correctly in the body. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children.

Peroxisomes are tiny components within cells. In some ways, they are like a cell's organs (organelles). Peroxisomes contain chemical substances called enzymes, such as catalase and peroxidase, that help the body break down (metabolize) fatty acids and hydrogen peroxide. When the enzymes do not work correctly, fatty acids and hydrogen peroxide build up, causing damage in many areas in the body.

There are different types of inherited disorders. In most peroxisomal disorders, both parents of the affected child carry a copy of the abnormal gene. Because usually two copies of the abnormal gene are necessary for the disorder to occur, usually neither parent has the disorder. Some peroxisomal disorders are X-linked, which means only one copy of the abnormal gene can cause the disorder in boys.

X-linked adrenoleukodystrophy

This is the most common peroxisomal disorder. It primarily affects the brain and spinal cord and the adrenal glands. Because the defective gene is on the X chromosome (one of the sex chromosomes), the disorder occurs almost entirely in boys (see figure X-Linked Recessive Disorders).

The cerebral form of X-linked adrenoleukodystrophy occurs between the ages of 4 years and 12 years. Children have symptoms of attention problems that progress over time to severe behavioral problems, dementia, and vision, hearing, and movement problems. This form causes total disability and death a few years after the diagnosis. Milder adolescent and adult forms have also been diagnosed.

Adrenomyeloneuropathy (AMN) is a milder form of this disease that occurs in a person's 20s or 30s. People have symptoms of stiffness, weakness, and pain in the legs that gets progressively worse over time. Problems with nerves cause the urinary sphincter (the muscular ring that keeps urine in the bladder until a person urinates) and sexual organs to stop working correctly. Some of these people also develop symptoms of the cerebral form.

People with any form of X-linked adrenoleukodystrophy may also develop underactive adrenal glands (glands on the kidneys that secrete hormones). Some people develop Addison disease but do not have brain and spinal cord problems.

Doctors diagnose X-linked adrenoleukodystrophy by doing magnetic resonance imaging (MRI) of the brain and by analyzing the blood to look for certain fatty acids. The diagnosis is confirmed by gene sequencing. Genetic testing, which is used to determine whether a couple is at increased risk of having a baby with a hereditary genetic disorder, is also available.

Some people may be helped by bone marrow transplantation or stem cell transplantation. People who have problems with their adrenal glands are given corticosteroids. A supplement of a mixture of glyceryl trioleate and glyceryl trierucate (called Lorenzo’s oil) can return fatty acid levels in the blood to normal and may help some people but is still being studied.

Zellweger syndrome (ZS), neonatal adrenoleukodystrophy, and infantile Refsum disease (IRD)

These three disorders are among a group of conditions called Zellweger spectrum disorders that have overlapping symptoms and affect many parts of the body. Zellweger syndrome is the most severe form, and infantile Refsum disease is the least severe form.

Zellweger syndrome and neonatal adrenoleukodystrophy occur in infancy. Refsum disease occurs later, even in adulthood in some people. Symptoms of these disorders may include distinctive facial features, brain and spinal cord defects, destruction of the tissues that wrap around nerves (demyelination), seizures (in newborns), and weak muscle tone (hypotonia). Children may have an enlarged liver and cysts on their kidneys. Children may also have short limbs, a specific bone abnormality called chondrodysplasia punctata (which affects the growth of the long bones), cataracts, abnormal growth of blood vessels in the eye (retinopathy), hearing loss, and weakness, numbness, and pain in the hands and feet. Physical activity such as movement and speech is slowed.

Doctors diagnose these disorders by testing the blood for certain fatty acids. Genetic testing is also available.

Refsum disease

In this disorder, phytanic acid, which is a product of fat metabolism, accumulates in tissues. A buildup of phytanic acid leads to nerve and retinal damage, hearing loss, loss of smell (anosmia), spastic movements, and changes in the bone and skin. Symptoms usually start in a person's 20s but may not start until later.

Doctors diagnose Refsum disease by testing the blood to determine whether the level of phytanic acid is elevated.

Treatment of Refsum disease involves avoiding eating foods that contain phytanic acid, including dairy products, beef and lamb, and fatty fish such as tuna, cod, and haddock. Plasmapheresis, in which phytanic acid is removed from the blood, may be helpful.

Rhizomelic chondrodysplasia punctata

Symptoms of rhizomelic chondrodysplasia punctata begin in infancy and include a sunken appearance of the middle of the face, strikingly short limbs, a prominent forehead, small nostrils, cataracts, scaling and flaking of the skin (ichthyosis), and a profound slowing of physical activity such as movement and speech. Defects of the spine are also common.

Doctors diagnose rhizomelic chondrodysplasia punctata by taking x-rays and testing the blood.

There is no effective treatment for rhizomelic chondrodysplasia punctata. However, infants who have high blood levels of phytanic acid should consume foods low in phytanic acid.

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