Summary about Disease
Deficiency of cobalamin (vitamin B12) processing refers to a group of inherited disorders that impair the body's ability to absorb, transport, or utilize cobalamin. This can lead to cobalamin deficiency despite adequate dietary intake. These defects affect various steps in cobalamin metabolism, leading to a buildup of precursor molecules and a lack of functional cobalamin coenzymes. Untreated cobalamin processing defects can cause serious neurological damage, developmental delays, and metabolic complications.
Symptoms
Symptoms vary depending on the specific type and severity of the cobalamin processing defect. Common symptoms include:
Failure to thrive (poor weight gain and growth)
Developmental delays
Hypotonia (decreased muscle tone)
Lethargy
Seizures
Megaloblastic anemia (abnormally large red blood cells)
Feeding difficulties
Neurological problems (e.g., ataxia, cognitive impairment)
Skin problems (e.g., hyperpigmentation)
Vision problems
Causes
Cobalamin processing defects are caused by genetic mutations affecting genes involved in:
Cobalamin absorption: Intrinsic factor deficiencies that prevents cobalamin absorption
Intracellular cobalamin transport: Transporters that move cobalamin inside the cell.
Cobalamin processing within cells: Enzymes that convert cobalamin into its active coenzyme forms (methylcobalamin and adenosylcobalamin). Specific genetic defects are classified into complementation groups (cblA, cblB, cblC, cblD, cblE, cblF, cblG, cblH, cblJ) based on the affected gene. The inheritance pattern is typically autosomal recessive, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
The primary treatment is high-dose cobalamin supplementation, typically given intramuscularly. The specific form and dosage of cobalamin depend on the type of defect.
Hydroxocobalamin: Often preferred, particularly in defects of cobalamin reduction (cblA, cblB).
Betaine: Can be used to reduce homocysteine levels in some defects (e.g., cblC).
Folic Acid: To help with anemia Medications to manage seizures and other complications might also be necessary.
Is Communicable
No. Cobalamin processing defects are genetic disorders and are not contagious or communicable. They are inherited, not transmitted from person to person.
Precautions
Genetic counseling: For families with a history of cobalamin processing defects, genetic counseling is recommended to assess the risk of recurrence in future pregnancies.
Newborn screening: In some regions, newborn screening may detect certain cobalamin processing defects, allowing for early intervention.
Adherence to treatment: Strict adherence to the prescribed cobalamin supplementation regimen is crucial to prevent or minimize complications.
Monitoring: Regular monitoring of blood levels of cobalamin, homocysteine, and methylmalonic acid is important to assess treatment effectiveness.
Dietary modifications: May be needed to supplement Vitamin B12 intake.
How long does an outbreak last?
These are not outbreaks as the disease is genetic, and therefore is ongoing for those who are affected.
How is it diagnosed?
Diagnosis typically involves:
Clinical evaluation: Assessment of symptoms, medical history, and family history.
Laboratory tests:
Complete blood count (CBC) to detect megaloblastic anemia.
Serum cobalamin levels: Can be normal or low.
Serum methylmalonic acid (MMA) levels: Elevated in some defects.
Serum homocysteine levels: Elevated in some defects.
Urine organic acid analysis: May show elevated methylmalonic acid or other abnormal metabolites.
Genetic testing: Confirmatory testing to identify specific gene mutations.
Enzyme assays: May be performed on fibroblasts to assess the activity of specific enzymes involved in cobalamin metabolism.
Timeline of Symptoms
The timeline of symptom onset can vary:
Early-onset: Some severe forms (e.g., cblC) manifest in infancy or early childhood with failure to thrive, neurological problems, and metabolic disturbances.
Late-onset: Other forms may present later in childhood or even adulthood with milder symptoms such as fatigue, cognitive impairment, or psychiatric problems.
Asymptomatic: Rarely, individuals with certain mutations may remain asymptomatic if the defect is mild or if they receive adequate dietary cobalamin.
Important Considerations
Early diagnosis and treatment are essential to prevent irreversible neurological damage and other complications.
Lifelong monitoring and treatment are usually required.
Variable expressivity: The severity of symptoms can vary even among individuals with the same genetic mutation.
Multidisciplinary care: Management often involves a team of specialists, including pediatricians, geneticists, neurologists, and nutritionists.
Research: Ongoing research aims to develop new treatments and improve understanding of these complex disorders.