Refsum disease

Refsum Disease: A Rare Genetic Disorder

Refsum disease, also known as adult Refsum disease or classic Refsum disease, is a rare genetic disorder that affects the body's ability to break down a type of fat called phytanic acid. This buildup of phytanic acid in the blood and tissues can cause a variety of symptoms, including:

• Vision loss: Due to an eye disorder called retinitis pigmentosa [1, 8]
• Absence of sense of smell (anosmia): A common symptom of Refsum disease [2, 4, 8]
• Nerve degeneration (peripheral neuropathy): A progressive condition that affects the nerves [3, 5]
• Muscle coordination problems (ataxia): Difficulty with balance and movement [4, 9]
• Bone and skin changes: Such as ichthyosis, a condition characterized by dry, scaly skin [4, 10]

Refsum disease is an autosomal recessive disorder, meaning that it is inherited from both parents in a recessive pattern. The disease is caused by genetic changes in the PHYH gene or the PEX7 gene, which affect the body's ability to break down phytanic acid [13, 14].

It's worth noting that Refsum disease can be diagnosed at any age, ranging from infancy to adulthood, and its symptoms can vary depending on the individual.

Common Signs and Symptoms of Refsum Disease

Refsum disease, also known as adult Refsum disease or infantile Refsum disease, is a rare genetic disorder that affects the body's ability to break down certain types of fat. The signs and symptoms of Refsum disease can vary in severity and progression, but here are some common ones:

• Vision Loss: One of the most frequent early symptoms of Refsum disease is loss of night vision (retinitis pigmentosa), which can progress to low vision or blindness [1][2].
• Absence of Sense of Smell: Many people with Refsum disease experience anosmia, a condition where they lose their sense of smell [3][4].
• Weakness and Numbness in Hands and Feet: Peripheral neuropathy, a degenerative nerve disease, can cause weakness and numbness in the hands and feet [5][6].
• Hearing Loss: Some individuals with Refsum disease may experience hearing loss [7][8].
• Balance and Coordination Problems: Ataxia, a condition that affects muscle coordination, can lead to balance and coordination problems [9][10].
• Skeletal Abnormalities: Refsum disease can also cause skeletal abnormalities, such as short metacarpals and metatarsals in the hands and feet [1].
• Cardiac Arrhythmia and Heart Failure: In some cases, Refsum disease can lead to cardiac arrhythmia and heart failure due to cardiomyopathy [11][12].

It's essential to note that the signs and symptoms of Refsum disease can appear and progress slowly, making it challenging to distinguish from other similar disorders. Biochemical and genetic testing can confirm the diagnosis after documenting clinical characteristics.

References:

[1] Signs & Symptoms. At birth, individuals with Refsum disease generally appear normal although they may show shorter bones in the hands and feet (metacarpals and metatarsals, respectively).

[2] 3. Apr 12, 2024 — Symptoms of Refsum disease · retinitis pigmentosa, or difficulty seeing in low light that can lead to vision loss

[3] Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.

[4] 9. Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.

[5] Symptoms. The most common symptoms of Refsum disease include: Retinitis pigmentosa: Retinitis pigmentosa is an expression of degenerative eye disease as the visual receptors are lost in the retina and the background structure of the eye is exposed.

[6] 8. Other symptoms may include deafness, weakness or numbness of the hands and feet (peripheral neuropathy), ataxia, and ichthyosis.

[7] Refsum disease is a rare genetic disorder that can lead to vision loss, weakness and numbness in your hands and feet, and hearing loss.

[8] 12. Signs and symptoms of Refsum disease are abundant but appear and progress slowly; therefore, it is essential to assess the chronology of symptoms to distinguish it from other potentially similar disorders.

[9] Refsum disease is a rare disorder of lipid metabolism that is inherited as a recessive trait. Symptoms may include a degenerative nerve disease (peripheral neuropathy), failure of muscle coordination (ataxia), retinitis pigmentosa, and bone and skin changes.

[10] Adult Refsum disease (ARD) is associated with elevated plasma phytanic acid levels, late childhood-onset (or later) retinitis pigmentosa, and variable combinations of anosmia, polyneuropathy, deafness, ataxia, and ichthyosis.

Refsum disease diagnosis involves various tests to confirm the presence of this rare genetic disorder. Here are some diagnostic tests used for Refsum disease:

• Blood test: A blood sample is taken to measure the levels of phytanic acid, a type of fat that accumulates in individuals with Refsum disease (2).
• Genetic testing: This is typically the most accurate way to confirm Refsum disease diagnosis. Genetic testing involves analyzing DNA samples from an individual or their family members to identify mutations in the PEX genes responsible for this condition (6, 5).
• Enzymatic fibroblast analysis: This test measures the activity of enzymes involved in breaking down phytanic acid. It can be used to confirm Refsum disease diagnosis and differentiate it from other conditions (4).
• Skin biopsy: In some cases, direct measurement of enzyme activities in skin biopsy samples may be required to confirm Refsum disease diagnosis (6).
• MRI findings: Magnetic Resonance Imaging (MRI) scans can reveal symmetrical signal changes involving the corticospinal tracts, cerebellar dentate nuclei, and corpus callosum, which are characteristic of Refsum disease (10).

These diagnostic tests help healthcare providers arrive at a diagnosis for Refsum disease. It's essential to note that the specific tests used may vary depending on an individual's age and symptoms.

References: (2) - High levels of phytanic acid in blood samples are indicative of Refsum disease. (4) - Enzymatic fibroblast analysis is useful for diagnosing patients with suspected Refsum disease. (5) - Genetic testing confirms the diagnosis by identifying mutations in the PEX genes. (6) - Direct measurement of enzyme activities in skin biopsy samples may be required to confirm Refsum disease diagnosis. (10) - MRI findings can reveal characteristic changes associated with Refsum disease.

Treatment Options for Refsum Disease

Refsum disease, also known as heredoataxia hemeralopica polyneuritiformis, is a rare genetic disorder that affects the metabolism of fatty acids. While there is no cure for this condition, various treatment options can help manage its symptoms and slow down its progression.

Dietary Restrictions

The primary treatment for Refsum disease involves limiting the intake of foods high in phytanic acid, which accumulates in the body due to a deficiency in the enzyme phytanoyl-CoA hydroxylase (PhyH). This includes:

• Beef and lamb
• Dairy products
• Fatty fish, such as cod, tuna, or haddock

Ideally, daily phytanic acid consumption should be less than 10-20 mg/day [1][5].

Medications

While there are no specific medications approved for the treatment of Refsum disease, certain drugs may help manage its symptoms. These include:

• Plasmapheresis: a treatment that involves removing excess phytanic acid from the blood
• Anti-arrhythmics and cardiac medication: to manage heart-related complications
• Hydrating creams: to treat skin symptoms

Other Treatment Options

In addition to dietary restrictions and medications, other treatment options may be considered on a case-by-case basis. These include:

• Bilateral cochlear implantation: for severe hearing loss
• Supportive care: to manage symptoms and improve quality of life

It's essential to note that Refsum disease is a rare condition, and treatment options may vary depending on individual circumstances.

References: [1] - Context 5 [2] - Context 4 [3] - Context 10 [4] - Context 11 [5] - Context 15

The differential diagnosis of Refsum disease involves considering other conditions that may present with similar symptoms. According to various sources [3, 10, 13], the following conditions should be considered in the differential diagnosis:

• Usher syndromes (types 1, 2, and 3)
• Alström syndrome
• Kearns-Sayre syndrome
• Sjögren-Larsson syndrome
• Citrin deficiency
• Zellweger spectrum disorder
• Multiple acyl-CoA dehydrogenase deficiency

These conditions can present with similar symptoms such as retinitis pigmentosa, sensorineural hearing loss, and ichthyosis. It is essential to assess the chronology of symptoms to distinguish Refsum disease from other potentially similar disorders [10].

In addition, adult Refsum disease (ARD) must remain part of the differential diagnosis, especially in cases where patients present with elevated plasma phytanic acid levels, late childhood-onset retinitis pigmentosa, and variable combinations of anosmia, polyneuropathy, deafness, ataxia, and ichthyosis [11].

A comprehensive evaluation, including physical examination, phytanic acid evaluation, and genetic studies, may contribute to reaching an accurate diagnosis for Refsum disease [14].