About phytanic acid storage disease
What is phytanic acid storage disease?
Refsum disease is one of a family of genetic disorders known as the leukodystrophies in which, as a consequence of the disruption of lipid metabolism, the myelin sheath that insulates and protects the nerves of the brain fails to grow. It is inherited as an autosomal recessive trait. It is characterized by progressive loss of vision (retinitis pigmentosa); degenerative nerve disease (peripheral neuropathy); failure of muscle coordination (ataxia); and dry, rough, scaly skin (ichthyosis).
The disorder is caused by the accumulation of a particular fatty acid (phytanic acid) in blood plasma and tissues. This occurs because of a malfunction of the gene that makes the enzyme that breaks down (metabolizes) this acid. The essential enzyme is absent.
Treatment with a diet low in foods that contain phytanic acid can be beneficial. Our bodies cannot make phytanic acid. Instead, it is introduced to the body in certain foods, including dairy products, beef, lamb and some seafood.
What are the symptoms for phytanic acid storage disease?
Increased night blindness due to retinal degeneration in late childhood or early adulthood (retinitis pigmentosa) symptom was found in the phytanic acid storage disease condition
At birth, individuals with Refsum disease generally appear normal although they may show shorter bones in the hands and feet (metacarpals and metatarsals, respectively). Between 10 and 20 years old, individuals may show their first symptom which is most frequently the loss of night vision (retinitis pigmentosa). Some people may not show any symptoms until up to 50 years of age. Retinitis pigmentosa occurs because light-sensing cells in the retina, a layer in the back of the eye, gradually deteriorate. The initial loss of night vision usually occurs during childhood, and the progression toward loss of peripheral vision and full Blindness may occur over the course of years.
Individuals with Refsum disease often present with retinitis pigmentosa and a combination of other symptoms. Other possible issues in the eye include abnormally small pupils, rapid, involuntary eye movement (nystagmus) and cloudiness in the eye that causes individuals to see starburst-type haloes around bright objects (cataracts). Individuals may experience a loss of their sense of smell and taste (anosmia) and after many years, deafness. Affected individuals also may experience numbness, weakness, a Tingling sensation or loss of reflexes in their hands and feet (peripheral polyneuropathy) associated with an unsteady gait (cerebellar ataxia) as they deteriorate. Additionally, individuals with Refsum disease may have rough, scaly patches of skin (ichthyosis) and general Weakness throughout the body. Shortening of bones in the hands and feet and abnormal growth plate formation affecting the knees, shoulders and elbows (skeletal dysplasia) may be seen. Although it is rare, if phytanic acid levels become very high in people with Refsum disease, then a cardiac arrhythmia (irregular heartbeat) can occur which could be life threatening.
The type and number of symptoms present in individuals with Refsum disease varies greatly from person to person and the severity depends on the level of phytanic acid in the body. If a person has a greater build-up of phytanic acid, they are expected to show more severe symptoms. The number and severity of symptoms also may increase with age.
What are the causes for phytanic acid storage disease?
Most cases (90%) of Refsum disease result from a change (mutation) in the PHYH gene. Most of the remaining cases result from a mutation in the PEX7 gene which transports PHYH into the peroxisomal compartment in cells. Mutations in PHYH and PEX7 genes cause abnormal functioning of peroxisomes, which are structures that allow for the breakdown of fatty acids, including phytanic acid. Specifically, PHYH codes for the phytanoyl-CoA hydroxylase enzyme that is used in the peroxisome to break down phytanic acid. Phytanic acid comes from the diet and is derived from bacterial fermentation of green plants or algae. It is commonly found in dairy, beef, lamb and other ruminant animal-derived food stuffs as well as some seafood. The improper functioning of the peroxisome and related enzymes means that phytanic acid cannot be broken down and thus accumulates in the cell. It is currently unclear how the buildup of phytanic acid is toxic and affects vision or how it causes other features of the disease.
Refsum disease is an autosomal recessive genetic disorder. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
What are the treatments for phytanic acid storage disease?
Treatment of Refsum disease requires minimizing intake of beef, lamb, certain seafood, and dairy products while maintaining carbohydrate intake, which helps prevent phytanic acid from entering the blood from fat or liver stores. Removal and reinfusion of blood (plasmapheresis or apheresis) may also be necessary if levels are very high or general symptoms such as profound weakness are present. Other treatments are tailored based on symptoms and are usually supportive measures. Patients with Refsum disease should avoid fasting and rapid weight loss because this causes release of phytanic acid stored in the body. Patients should using ibuprofen as this may interfere with the degradation pathway of phytanic acid.
Patients should receive guidance from a trained dietician and physician on how to minimize risks of acute phytanic acid release and how to manage a low phytanic acid diet.
Genetic counseling is recommended for affected individuals and their family members.
What are the risk factors for phytanic acid storage disease?
Phytantic acid storage disease is a rare genetic disorder. It is also known as Adult Refsum Disease (ARD) and results in numbness or weakening in the hands and feet (peripheral neuropathy).
Risk factors-
- This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
- The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
- The condition is more common in males than in females as it is an autosomal recessive disorder.
- This disease does not have any specific ethnic predisposition it is found across the world.
- Though this disease develops in childhood, some may not develop the symptoms till the late 40s.
- Dietary causes may also be seen. Phytanic acid comes from the diet and is derived from the bacterial fermentation of green plants or algae. It is also commonly found in dairy, beef, lamb, and other ruminant animal-derived foodstuffs and some seafood.
Conditions
Increased night blindness due to retinal degeneration in late childhood or early adulthood (retinitis pigmentosa),Deafness,Anosmia,Ataxia,Dry and scaly skin (ichthyosis)
Drugs
Diet control,Symptomatic treatment and plasmapheresis,Blood replacement therapies
Symptoms
Deafness,Anosmia,Ataxia,Dry and scaly skin (ichthyosis),Irregular heartbeat
Is there a cure/medications for phytanic acid storage disease?
Phytantic acid storage disease also known as adult Refsum disease (ARD) results in numbness or weakening in the hands and feet (peripheral neuropathy). it is a rare genetic disorder usually caused by an autosomal recessive condition.
Treatments:
- Individuals with Phytantic acid storage disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock.
- Grass feeding animals and their milk are also avoided.
- The primary treatment for ARD is to restrict or avoid foods that contain phytanic acid, including dairy products; beef and lamb; and fatty fish such as tuna, cod, and haddock.
- Some individuals may also require plasma exchange in which blood is drawn, filtered, and reinfused back into the body, to control the buildup of phytanic acid.
- Other treatments are tailored based on symptoms and are usually supportive measures.
- Patients should use ibuprofen as this may interfere with the degradation pathway of phytanic acid.
- Patients should receive guidance from a trained dietician and physician on how to minimize risks of acute phytanic acid release and how to manage a low phytanic acid diet.
- Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid.
Conditions
Increased night blindness due to retinal degeneration in late childhood or early adulthood (retinitis pigmentosa),Deafness,Anosmia,Ataxia,Dry and scaly skin (ichthyosis)
Drugs
Diet control,Symptomatic treatment and plasmapheresis,Blood replacement therapies
Symptoms
Deafness,Anosmia,Ataxia,Dry and scaly skin (ichthyosis),Irregular heartbeat