Imerslund-Grasbeck disease

BACKGROUND

Imerslund-Grasbeck disease, also called familial selective vitamin B12 malabsorption, is a rare inherited disorder that causes deficiencies in vitamin B12. The body is unable to absorb this vitamin from foods, such as fish, shellfish, meats, and dairy products.

Symptoms of the disorder usually develop four months to several years after birth. Because vitamin B12 is needed to produce healthy blood cells, patients with Imerslund-Grasbeck disease typically produce fewer and abnormally large red blood cells (called megaloblasts). This condition is commonly called megaloblastic anemia.

Some patients may also develop frequent infections and mild proteinuria (high amounts of protein in the urine) with no signs of kidney disease. If left untreated, patients may develop neurological problems, which may lead to permanent brain damage.

Researchers estimate that Imerslund-Grasbeck disease affects only six out of 1,000,000 people. To date, only about 300 cases have been reported worldwide, primarily in eastern Mediterranean countries.

Imerslund-Grasbeck disease can be successfully treated with lifelong supplements of vitamin B12. Because the patient is unable to absorb the vitamin in the small intestine, it must be injected.

Although treatment corrects the vitamin B12 deficiency, proteinuria is still present in patients who experience this condition. The symptoms of proteinuria are not a cause for concern because proteinuria will not worsen over time, and it does not indicate kidney damage.

CAUSES

Imerslund-Grasbeck disease is inherited as an autosomal recessive disorder. This means a person needs to inherit one mutated gene from each parent in order to develop the disorder.

Individuals who only have one mutated gene and do not experience symptoms are called carriers. Carriers have a 50% chance of passing the abnormal gene to each of their children. If just one parent is a carrier, the child will not develop the disorder, but there is a 50% chance that the child will be a carrier as well. If both parents are carriers, there is a 25% chance that each of their children will inherit the disease and a 50% chance that each of their children will be a carrier.

SIGNS AND SYMPTOMS

Megaloblastic anemia: Vitamin B12 is needed to produce normal levels of healthy red blood cells. Since people with Imerslund-Grasbeck disease are unable to absorb vitamin B12, they produce fewer and abnormally large red blood cells. This condition, called megaloblastic anemia, may cause symptoms, such as fatigue, pale skin, fast heartbeat, shortness of breath, chest pain, dizziness, cognitive problems, headache, and numb or cold sensations in the extremities.

Neurological problems: Studies have shown that a deficiency of vitamin B12 can lead to abnormal neurologic and psychiatric symptoms. These symptoms may include ataxia (shaky movements and unsteady manner of walking), muscle weakness, spasticity, incontinence, low blood pressure, vision problems, dementia, psychoses, and mood disturbances. Researchers report that these symptoms may occur when vitamin B12 levels are just slightly lower than normal and are considerably above the levels normally associated with anemia.

Proteinuria: Proteinuria, or high amounts of protein in the urine, occurs in roughly half of patients with Imerslund-Grasbeck disease. Patients who experience proteinuria have defects in their multi-ligand receptor cubilin. As a result, higher-than-normal amounts of protein are excreted in the urine. Proteinuria may cause urine to appear foamy. Proteinuria is normally associated with kidney problems. However, patients with Imerslund-Grasbeck disease and proteinuria do not appear to experience kidney problems.

DIAGNOSIS

Blood test: If a patient has symptoms of vitamin B12 deficiency, a blood test is typically performed. Low levels of the vitamin indicate a deficiency. Healthy individuals typically have 200-900 picograms of vitamin B12 per milliliter of blood. A deficiency is indicated when a person has less than 100 picograms of vitamin B12 per milliliter of blood.

Schilling test: A healthcare provider will then determine if the patient is able to absorb the vitamin. A test, called the Schilling's urinary excretion technique, is typically performed. During this test, a small dose of cobalamin is tagged with a radioactive substance and given to the patient by mouth. Then a large dose of non-radioactive cobalamin is injected into the patient. If the intestines absorb vitamin B12 normally, up to 25% of the swallowed vitamin will be passed in the urine. If the amount of radioactive cobalamin that is excreted in the urine is lower-than-normal, it indicates that the cobalamin was not properly absorbed.

If cobalamin is not properly absorbed, the test is usually repeated using intrinsic factor with the test dose. The intrinsic factor is a substance that is needed to absorb vitamin B12. This test rules out the possibility that the patient's absorption problem is caused by a lack of intrinsic factor. If the patient is still unable to properly absorb the vitamin despite the added intrinsic factor, Imerslund-Grasbeck disease may be indicated.

DNA test: If Imerslund-Grasbeck disease is suspected, a genetic test is performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the mutated genes associated with the disorder.

TREATMENT

General: Imerslund-Grasbeck disease can be successfully treated with life-long supplements of vitamin B12. Proteinuria still persists despite treatment. However, proteinuria is not a cause for concern because it will not worsen over time, and it does not indicate kidney damage in these patients.

An early diagnosis and prompt treatment is essential for patients with Imerslund-Grasbeck disease. If left untreated, low levels of vitamin B12 may lead to permanent neurological problems, including brain damage.

Vitamin B12 (cobalamin): Patients with Imerslund-Grasbeck disease receive intramuscular injections of vitamin B12 injections for the rest of their lives. Patients typically receive 1 milligram of a vitamin B12 supplement, called hydroxocobalamin, daily for 10 days. This treatment is repeated once a month for life.

INTEGRATIVE THERAPIES

Unclear or conflicting scientific evidence:

Vitamin B12: Administering vitamin B12 intramuscularly seems to be effective for treating selective vitamin B12 malabsorption (Imerslund-Grasbeck disease). Although this is considered the standard treatment for Imerslund-Grasbeck disease, additional research is needed to confirm its effectiveness.

Vitamin B12 is generally considered safe when taken in amounts that do not exceed the recommended dietary allowance (RDA). Avoid vitamin B12 supplements if allergic to cobalamin, cobalt, or any other product ingredients. Avoid with coronary stents or Leber's disease. Use cautiously if undergoing angioplasty.

PREVENTION

Although there is currently no known way to prevent Imerslund-Grasbeck disease, the risk of developing the condition is extremely low. Individuals who have a family history of the condition may undergo genetic testing to determine if they are carriers of the disorder.

Genetic counselors can help patients understand the risks of having a child with the disorder. He/she can also help patients understand the results of their tests.

An early diagnosis and prompt treatment is essential for patients with Imerslund-Grasbeck disease. If left untreated, low levels of vitamin B12 may lead to permanent neurological problems, including brain damage.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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