High vitamin B12 levels

Background

Elevated serum levels of vitamin B12 are a frequent and underestimated anomaly. Medical conditions that can increase vitamin B12 levels include liver disease, kidney failure and a group of blood cancers.

MethylmalonicAcidemia (MMA) is an inborn error of vitamin B12 metabolism that occurs mainly in neonates and less frequently during childhood or adolescence. The cblC, cblF and cblJ defects affect both the homocysteine-methionine and the methylmalonic acid cycle.

Case study

A 13-year-old primary care female patient presented with elevated serum vitamin B12 levels without supplementation. She is in the low growth percentile and a picky eater but she eats foods with vitamin B12. The determination of methylmalonic acid was performed to discard metabolopathy.

Results

Vitamin B12 measurement showed a persistent elevation of 2000 pg/ml (187-883), which was confirmed in another laboratory. Macro-B12 interference (macroforms) or interference by heterophile antibodies was ruled out. Urine methylmalonic acid was measured to rule out an inborn error of metabolism and was 774.5 mmol/mol creatinine (8). Plasma homocysteine was 81.3 µmol/l (5-15). The laboratory tests suggested MMA. The patient was treated with hydroxocobalamin. Genetic evaluation of MMA-associated genes was performed identifying two heterozygous MMACHC mutations, c.331C>T (p.Arg111Ter) and c.565C>A (p.Arg189Ser). These mutations were previously described as pathogenic and confirmed the diagnosis of MMA.

Discussion

Persistent hypercobalaminemia may be a cause for concern, but it is important to measure methylmalonic acid levels to discard a metabolic disorder. The diagnosis of MMA is complex and requires multispecialty care for diagnosis and treatment. Early diagnosis and treatment of asymptomatic patients are important to prevent complications, Integrating laboratory data with clinical presentation and family studies.