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Peroxisomal Disorders


Matt Demczko

, MD, Mitochondrial Medicine, Children's Hospital of Philadelphia

Reviewed/Revised Dec 2021 | Modified Aug 2023

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 Fatty acids Carbohydrates, proteins, and fats are the main types of macronutrients in food (nutrients that are required daily in large quantities). They supply 90% of the dry weight of the diet and 100%... read more 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 Inheritance of Single-Gene Disorders Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or code for functional RNA molecules.... read more . 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 X-Linked Recessive Disorders X-Linked Recessive Disorders , 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 X-Linked Recessive Disorders 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 Adrenal Insufficiency In adrenal insufficiency, the adrenal glands do not produce enough adrenal hormones. Adrenal insufficiency may be caused by a disorder of the adrenal glands, a disorder of the pituitary gland... read more Adrenal Insufficiency but do not have brain and spinal cord problems.

Some people may be helped by bone marrow transplantation or stem cell transplantation Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more . 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 Seizures in Children Seizures are a periodic disturbance of the brain’s electrical activity, resulting in some degree of temporary brain dysfunction. When older infants or young children have seizures, they often... read more (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 suspect these disorders when elevated levels of certain fatty acids are detected in the blood. Genetic testing is done to confirm the diagnosis.

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 Ichthyosis Ichthyosis is scaling and flaking of the skin that ranges from mild but annoying dryness to severe and disfiguring skin disease. (See also Itching and Dry Skin (Xeroderma).) Ichthyosis is a... read more 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.

More Information

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