Methylmalonic Aciduria, cblA Type

Alternative Names

  • Methylmalonic Acidemia, cblA Type
  • Methylmalonic Aciduria, Vitamin B12-Responsive, due to Defect in Synthesis of Adenosylcobalamin, cblA Type
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

251100

Mode of Inheritance

Autosomal recessive

Gene Map Locus

4q31.21

Description

Methylmalonic acidemia is an autosomal recessive disorder, caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase, a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin, or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of this condition is usually in early infancy, and it varies from mild to life threatening. Its manifestations include: lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, muscle hypotonia, hepatomegaly and coma. Diagnosis is based on analysis of organic acids in plasma and/or urine by gas-liquid chromatography and mass spectrometry. Also, uncovering this condition through neonatal screening for propionylcarnitine and/or increased propionylcarnitine-to-acetylcarnitine ratio in dried blood spots by tandem mass spectrometry (MS/MS) has become common. Treatment includes a protein-restricted diet, increased calories via high glucose-containing fluids and insulin to arrest catabolism; and monitoring serum electrolytes and ammonia, venous or arterial blood gases, and urine output. Patients with this type are responsive to vitamin B12. 

Molecular Genetics

Methylmalonic aciduria, cblA type is caused by mutations in the MMAA gene which contains 7 exons and spans about 17.1 kb. This gene gives instructions for making an enzyme called adenosylcobalamin (AdoCbl), which is necessary for the normal function of methylmalonyl CoA mutase enzyme. This enzyme helps break down certain proteins, lipids, and cholesterol. Mutations in the MMAA gene reduce the activity of methylmalonyl CoA mutase, leading to methylmalonic acidemia.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Organic acidopathies were diagnosed in 48 out of 248 cases (19%). Among them, nine cases from three families were found to have Methylmalonic acidemia due to cobalamin B deficiency, two cases from two families with mutase deficiency and three cases from three families of unknown type.   Methylmalonic academia accounts for 27% of all cases of organic acidopathies found in this cohort. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.

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