Fisiopatologia da deficiência de vitamina B12 e seu diagnóstico laboratorial / Physiopathology of vitamin B12 deficiency and its laboratorial diagnosis

INTRODUÇAO: A vitamina B12 é hidrossolúvel, não-sintetizada pelo organismo humano, presente em alimentos de origem animal. Sua deficiência é muito freqüente entre idosos, vegetarianos e indivíduos que adotam baixa dieta protéica ou apresentam problemas de absorção gastrintestinal. FISIOPATOLOGIA: A deficiência de vitamina B12 leva a transtornos hematológicos, neurológicos e cardiovasculares, principalmente, por interferir no metabolismo da homocisteína (Hcy) e nas reações de metilação do organismo. Muitas vezes a deficiência pode permanecer assintomática por longos períodos, desencadeando uma deficiência crônica que, se mantida, pode levar a manifestações neurológicas irreversíveis. METODOLOGIAS: Metodologias eficientes que permitam um diagnóstico precoce são imprescindíveis. Porém um método considerado padrão-ouro ainda não é consensual. A dosagem sérica de vitamina B12 sofre algumas restrições pelos problemas de sensibilidade e especificidade, podendo ocorrer sintomas de deficiência mesmo com vitamina B12 sérica dentro dos níveis normais ou, de outro modo, ocorrendo baixos níveis de vitamina B12 sérica sem, contudo, apresentar baixos níveis da fração de vitamina realmente disponível para as células e sem apresentar sintomatologia. Novas alternativas vêm surgindo, como a dosagem de transcobalamina II (Tc II), a única fração de vitamina B12 disponível para as células, ou a dosagem de ácido metilmalônico (MMA) e Hcy, metabólitos que aumentam quando ocorre diminuição de vitamina B12 intracelular. Estes testes apresentam algumas vantagens, mas também limitações importantes para uso rotineiro. CONCLUSAO: Em casos subclínicos, um diagnóstico correto e precoce representa ainda um desafio, e futuros estudos são necessários para definir um método padrão para diagnóstico laboratorial da deficiência de vitamina B12.

High prevalence of cobalamin deficiency in Guatemalan schoolchildren: associations with low plasma holotranscobalamin II and elevated serum methylmalonic acid and plasma homocysteine concentrations.

BACKGROUND: Studies conducted in Guatemala, Mexico, and Venezuela have found high prevalences of low plasma cobalamin (vitamin B-12) concentrations in infants and children. It is not known whether these low cobalamin concentrations are accompanied by altered metabolic functions. OBJECTIVE: We sought to assess the prevalence of cobalamin deficiency in Guatemalan children by using sensitive and specific markers of deficiency. DESIGN: Children (n = 553) were screened for low plasma cobalamin. Those with low plasma cobalamin (< 162 pmol/L) were matched by age, grade, and sex to those with marginal (162-221 pmol/L) and adequate (> 221 pmol/L) concentrations. In this matched subset (n = 180), additional biochemical indicators of cobalamin deficiency were measured. RESULTS: Of the 553 children screened, 11% had low plasma cobalamin and an additional 22% had marginal concentrations. The prevalences of elevated serum methylmalonic acid (MMA), plasma homocysteine, or both were significantly higher in children with low and marginal plasma cobalamin than in children with adequate plasma cobalamin. Mean serum MMA was high in all groups compared with values reported in other populations. Mean plasma holotranscobalamin II concentrations were significantly lower in children with low rather than marginal or adequate plasma cobalamin. However, holotranscobalamin II was a less sensitive indicator of cobalamin depletion than was MMA. CONCLUSION: Biochemical markers of cobalamin deficiency confirmed that the cobalamin status of children with low and marginal plasma cobalamin is inadequate to support normal metabolic function.

Predictors of cobalamin deficiency in Guatemalan school children: diet, Helicobacter pylori, or bacterial overgrowth?

OBJECTIVES: The authors investigated whether low vitamin B12 intake, impaired gastric function, infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children. METHODS: The plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and and bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests, respectively. RESULTS: infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin. CONCLUSIONS: The specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Immunofluorescent localization of vitamin B12-binding protein from sow's milk in the ileal mucosa of piglets.

Studies in vitro have shown that the vitamin B12-binding protein from sow's milk enhances vitamin B12 absorption by the neonatal piglet. In the present paper, localization of the milk vitamin B12 binding protein on the brush border membrane of intact ileal enterocytes was demonstrated by an immunocytochemical procedure in which the binding protein was incubated within isolated loops of ileum of anesthetized neonatal piglets.