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Methylmalonic Aciduria Type CblB, Genetic Testing

CblB type methylmalonic aciduria is a subtype of methylmalonic acidemia (MMA), a rare genetic disorder characterized by the inability to break down certain proteins and fats. Like other forms of MMA, it is considered an inborn error of metabolism, and it involves defects in the enzymes or cofactors necessary for the metabolism of vitamin B12 (cobalamin).

CblB type methylmalonic aciduria genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

The key features and aspects of cblB type methylmalonic aciduria include:

  • Genetic Basis: CblB type methylmalonic aciduria is caused by mutations in the MMAB gene. The MMAB gene provides instructions for producing a protein that plays a crucial role in the metabolism of vitamin B12.
  • Vitamin B12 Metabolism: Vitamin B12 is essential for breaking specific amino and fatty acids. In cblB type methylmalonic aciduria, mutations in the MMAB gene result in impaired processing of vitamin B12, leading to the accumulation of methylmalonic acid.
  • Clinical Presentation: Individuals with cblB type methylmalonic aciduria may present with a range of symptoms, including feeding difficulties, failure to thrive, developmental delays, intellectual disability, and neurological symptoms. The severity of symptoms can vary.
  • Metabolic Crisis: Methylmalonic acidemia, including cblB type, is associated with the risk of metabolic crises. These crises can be triggered by infections, stress, or periods of fasting, and they may lead to severe complications.
  • Diagnostic Testing: Diagnosis is typically confirmed through biochemical testing, which reveals elevated levels of methylmalonic acid in blood and urine. Genetic testing can identify mutations in the MMAB gene, confirming the specific subtype.
  • Treatment: Management of cblB type methylmalonic aciduria involves a combination of dietary measures and medical interventions. Vitamin B12 supplementation is a key component of treatment to improve the conversion of methylmalonyl-CoA to succinyl-CoA. Additionally, dietary restrictions may be recommended to limit the intake of certain amino acids.
  • Lifelong Management: Individuals with cblB type methylmalonic aciduria require ongoing management to prevent metabolic crises and minimize the disorder's impact on their health. Regular medical monitoring and follow-up with metabolic specialists are essential.
More Information

Methylmalonic acidemia type cblB is a rare autosomal recessive disease caused by mutations in the MMAB gene on chromosome 12q24. The disease can develop either by homozygosis (the presence of two copies) of a pathogenic mutation or compound heterozygosis (the presence of two different pathogenic mutations, each on one chromosome).

The MMAB gene codes for the mitochondrial ATP enzyme cobalamin adenosyl transferase. This enzyme is involved in the synthesis of adenosylcobalamin, a coenzyme of methylmalonyl-CoA mutase (mut).

Although methylmalonic aciduria type cblB is an autosomal recessive disease, it has been observed that the presence of a single copy of the c.700C>T variant (also called p.Gln234Ter) could produce symptoms, although less severe than if present in homozygosis (2 copies). In addition, patients with this mutation respond moderately to supplementation with hydroxycobalamin (vitamin B12 in its active form).

CblB type methylmalonic aciduria genetic testing analyzes the 8 most frequent pathogenic mutations of the MMAB gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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