Methylmalonic acidemia with homocystinuria
Dernière mise à jour 16 mai 2023
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Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. The body is also unable to convert the amino acid homocysteine to another amino acid, methionine. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. There are several forms of this combined condition, and the different forms have different genetic causes and signs and symptoms. The most common and best understood form, called cblC type (or cobalamin C disease), occurs in about 80 percent of affected individuals.
Description
Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. The body is also unable to convert the amino acid homocysteine to another amino acid, methionine. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. There are several forms of this combined condition, and the different forms have different genetic causes and signs and symptoms. The most common and best understood form, called cblC type (or cobalamin C disease), occurs in about 80 percent of affected individuals.
The signs and symptoms of methylmalonic acidemia with homocystinuria usually develop in infancy, although they can begin at any age. When the condition begins early in life, affected individuals typically grow more slowly than expected. This sign is sometimes iedentified before the baby is born. These infants can also have difficulty feeding and have an abnormally pale appearance (pallor). Eye abnormalities and neurological problems, including weak muscle tone (hypotonia) and seizures, are also common in people with methylmalonic acidemia with homocystinuria. Many infants and children with this condition have delayed development and intellectual disability, and some have an unusually small head size (microcephaly).
Some people with methylmalonic acidemia with homocystinuria develop a blood disorder called megaloblastic anaemia. Megaloblastic anaemia occurs when a person has a low number of red blood cells (anaemia), and the remaining red blood cells are larger than normal (megaloblastic). The signs and symptoms of early-onset methylmalonic acidemia with homocystinuria worsen over time, and the condition can be life-threatening if it is not treated.
When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, it may change an affected person's behaviour and personality; the person may become less social and may experience hallucinations, delirium, and psychosis. In addition, these individuals can begin to lose previously acquired mental and physical abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). Some people with methylmalonic acidemia with homocystinuria whose signs and symptoms begin later in life develop a condition called subacute combined degeneration of the spinal cord, which leads to numbness and weakness in the lower limbs, difficulty walking, and frequent falls.
Inheritance patterns
The source lists the following possible inheritance patterns: X-linked recessive; Autosomal recessive. More than one pattern can apply in different cases.
Related genes
Other names
Methylmalonic acidemia and homocystinemia
Methylmalonic acidemia and homocystinuria
Methylmalonic aciduria and homocystinuria
Vitamin B12 metabolic defect with combined deficiency of methylmalonyl-coA mutase and homocysteine:methyltetrahydrofolate methyltransferase
Vitamin B12 metabolic defect with combined deficiency of methylmalonyl-coA mutase and methionine synthase activities
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Lectures complémentaires et références
- Methylmalonic acidemia with homocystinuria; MedlinePlus, National Library of Medicine.
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