The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid

Abstract

Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non-cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.

Response of early weaned piglets to graded levels of dietary cobalamin

“…Our results provide evidence that an inadequate intake of cobalamin during the first 15 d postweaning, leads to the progressive depletion of body cobalamin stores, as reflected by reductions in plasma cobalamin and increases in plasma homocysteine. Other research groups have documented the sensitivity of plasma and tissue cobalamin (Stangl et al 2000) and plasma homocysteine and methylmalonic acid (Stabler et al 1986(Stabler et al , 1988(Stabler et al , 1997Chu and Hall 1988;Allen et al 1990;Lindenbaum et al 1990;Moelby et al 1990;Savage et al 1994;Bolann et al 2000), and growth (Neumann et al 1950a,b;Stangl et al 2000) to cobalamin status. However the novelty of the current work involves the use of plasma homocysteine, in conjunction with plasma cobalamin, for the assessment of cobalamin requirements in animals, specifically the earlyweaned pig.…”

“…Methionine synthase, an enzyme of ubiquitous distribution, catalyzes the remethylation of the sulfur amino acid homocysteine to form methionine. Methylmalonyl-CoA mutase catalyzes the conversion of L-methylmalonyl-CoA to succinyl-CoA and, as such, plays a critical role in anaplerosis of the tricarboxylic acid cycle, gluconeogenesis and the regulation of ATP synthesis (Nelson and Cox 2000). A deficiency of dietary cobalamin leads to depressed tissue and plasma cobalamin concentrations (Stangl et al 2000).…”

“…These estimates are based on extrapolations from studies with heavier, older pigs conducted over 40 yr ago (Anderson and Hogan 1950;Nesheim et al 1950;Richardson et al 1951;Frederick and Brisson 1961). The movement to earlier weaning dates and the development of leaner, faster-growing genotypes over the past few decades necessitate a review of the adequacy of current recommendations for this watersoluble vitamin.…”

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over

“…Following the early studies that demonstrated the basic relationship between vitamin B 12 and MMA in man (Gompertz et al, 1967;Chanarin et al, 1973;Norman et al, 1982;Carmel, 2000), and which established reliable assay techniques for MMA (Stabler et al, 1986), were a number of key studies showing a surprisingly high prevalence of raised MMA levels in the plasma of older people, where it appeared to provide a more reliable indicator of functional vitamin B 12 status than serum or plasma vitamin B 12 concentrations per se (Lindenbaum et al, 1988;Rasmussen et al, 1989;Moelby et al, 1990;Joosten et al, 1993;Allen & Casterline, 1994;Lindenbaum et al, 1994;Koehler et al, 1996;Baik & Russell, 1999;Bjorkegren & Svardsudd, 1999;Herrmann et al, 2000). Clearly, the ageing process in itself, and the increasing prevalence of age-related medical conditions that impair vitamin B 12 absorption, both increase the probability that people will become vitamin B 12 -deficient as they grow older.…”

Diagnosis of Cobalamin Deficiency: The Old and the New

“…Renal failure may be possible (Rasmussen et al, 1990b) as an explanation in the occasional subject with raised MMA. Moelby et al (1990) also concluded that the serum MMA level was a sensitive and specific indicator of Cbl deficiency and should replace the non-specific Cbl assay. Indeed, they claim it is unecessary for the patient to be subjected to a Schilling test and bone marrow aspirate, although it is to their credit that they did both.…”