Relationship between the Levels of Holotranscobalamin and Vitamin B12 / 대한진단검사의학회지

To date, the determination of serum vitamin B12 levels has been the most common laboratory test for the assessment of vitamin B12 status; however, the diagnostic accuracy of this test is low. To obtain a more sensitive marker, a new test to measure holotranscobalamin (holoTC) levels has been introduced. In this study, we assessed 45 patients for whom a vitamin B12 test had been requested and 139 anemic patients. We investigated the associations between the levels of homocysteine (Hcy) and those of holoTC, serum vitamin B12, and folate and assessed the diagnostic value of holoTC levels as a marker for vitamin B12 deficiency. We also determined the precision of the AxSYM holoTC assay by calculating the coefficient of variance (CV). The within-run and between-run precision values were excellent, as all CV values were less than 3.5%. The holoTC levels were low (12 micromol/L) indicated vitamin B12 deficiency. Thus, the holoTC levels were more sensitive than the serum vitamin B12 levels for indicating vitamin B12 status. If the serum vitamin B12 level is 151-300 pmol/L, the levels of holoTC alone or in combination with serum vitamin B12 levels are likely to be more useful markers than serum vitamin B12 levels alone.

Study on serum transcobalamin II in patients with murine typhus.

We measured the serum transcobalamin II in murine typhus- infected patients (n = 16) admitted to the Hospital for Tropical Diseases in 1996-1997, compared with healthy controls (n = 60). The results showed that the transcobalamin II (TCII) and total serum unsaturated vitaminB12 binding capacity (UBBC) in patients with murine typhus (2,126.5 pg/ml, range 1,262-4,568 and 3,771.5 pg/ml, range 1,576-6,763 pg/ml) were statistically significantly higher than normal subjects (987.5 pg/ml, range 678-2,000 pg/ml and 1,402 pg/ml, range 932-2,470 ml) (p<0.001). Serum TCII levels in patients (63%) were elevated during the febrile period and returned to normal post-treatment. These findings suggest that patients with murine typhus had stimulation of reticulo-endothelial system, spleen, mesenteric lymph nodes, liver and skin and then released TCII into the blood circulation. The elevation in TCII may be used for confirming a diagnosis of murine typhus.

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.

Elevation of serum transcobalamin II in patients with scrub typhus.

Serum transcobalamin II levels were measured in scrub typhus patients. Eighteen out of fifty-two patients admitted to Maharat Nakhon Ratchasima Hospital were diagnosed with scrub typhus infection. The serum unsaturated vitamin B12 binding protein (UBBC) and total vitamin B12 binding protein (TBBC) levels in these patients were significantly higher than in normal subjects (p < 0.001). The mean serum transcobalamin II level in the typhus patients was also significantly higher than in the normal subjects (p=0.004). There was a significant correlation between serum TCII levels and typhus IgM or IgG titers (p < 0.05), but not to total IgM levels. These findings indicate that patients with scrub typhus had stimulation of the recticuloendothelial system as a result of a considerable increase in transcobalamin II levels.

Serum transcobalamin II level in glucose-6-phosphate dehydrogenase deficient subjects with typhoid fever.

Transcobalamin II (TCII) is the vitamin B12 binding protein which is responsible for delivery of this vitamin to the tissues. High values for serum TCII have been reported in many clinical conditions. This paper describes the elevated serum TCII levels in three G-6-PD deficient patients with typhoid fever. They had severe hemolysis with hemoglobinuria associated with slight liver dysfunctions but without obvious increased serum creatinine and BUN concentrations. A remarkable increase in serum TCII level was observed during active hemolysis and decreased to the normal level within 2-3 days after hemolysis ceased. The mechanism of increased serum TCII during hemolysis is probably due to hemoglobinuria secondary to excessive hemolysis. As Hb is known to be efficiently reabsorbed by the proximal tubule cells and can competitively inhibit the tubular uptake of TCII-B12. It is possible that excess Hb interferes with TCII uptake and degradation at renal tubular cells. Therefore, the circulating TCII survival is prolonged resulting in the elevated TCII level. Furthermore, lysosomal degradation of newly synthesized TCII is a normal process that regulates the TCII secretion. Therefore, a reduced lysosome-mediated uptake of TCII-B12 by renal tubular cell may stimulate the TCII secretion as has been shown experimentally in vitro.

Abnormally elevated serum transcobalamin II levels in patients with cerebral malaria.

Transcobalamin II (TCII) levels have been reported to be elevated in patients with many clinical conditions including proliferative reticuloendothelial system. As reactive macrophage hyperplasia frequently occurs in patients with malaria, the objective of the present study was to determine TCII in patients with Plasmodium falciparum with cerebral symptoms. The studies were performed on 14 cerebral malaria patients as well as 60 normal subjects. The mean values of serum vitamin B12 and TCII levels were significantly higher in the patient group and 6 and 7 patients had serum vitamin B12 and TCII levels higher than the normal values. There was direct relationship between serum TCII levels and BUN or creatinine levels. These findings indicated that raised serum TCII level occurred only in patients with renal insufficiency. A decreased glomerular fiLtration rate reduced the amount of vitamin B12 and TCII-B12 that filtered through the glomeruli resulting in the reduced proximal tubular cells uptake and its degradation of TCII. This reduced lysosomal enzyme activity, therefore, prolongs the intravascular TCII survival and increased secretion of TCII into the circulation. Therefore, serum TCII levels were elevated in these cerebral malaria patients.

Folic acid, vitamin B12 and vitamin B12 binding proteins in patients with neuroblastoma.

Serum vitamin B12, serum and red cell folate and serum vitamin B12 binding proteins were determined in 18 patients with neuroblastoma, with ages ranging from 8 months to 14 years. A mean value of serum vitamin B12 level was slightly but not significantly lower than that of the normal subjects but all of them had serum vitamin B12 levels over 150 pg/ml. There was no relationship between serum vitamin B12 levels and hemoglobin, hematocrit or white cells. Transcobalamin I (TCI) was significantly increased resulting in slightly elevated UBBC and normal TBBC levels in these patients. This could be a compensatory mechanism for the low serum vitamin B12 by increasing the unsaturated vitamin B12 binding capacity of TCI. All these findings indicated that the status of vitamin B12 in patients with neuroblastoma was within the normal limits. Treatment of neuroblastoma by giving a high dose of vitamin B12 would therefore not give any direct therapeutic effect. Both serum and red cell folate concentrations were significantly lower in the group of patients. As only 2 out of 18 patients had low serum folate and none of them had red cell folate lower than the lower limit of normal subjects; therefore these patients were only in the state of negative folate balance.

Serum vitamin B 12 and folic acid levels in patients with fasciolopsiasis.

Serum vitamin B12, serum and red cell folate concentrations and vitamin B12 absorption were studied in 100 patients with fasciolopsiasis. A mean value of serum vitamin B12 level in the patient group was found to be significantly lower than that of normal subjects and 14% of these patients had serum vitamin B12 level less than 100 pg/ml. Serum UBBC and TBBC levels in the patients were significantly higher than those of the normal subjects. Serum TCI and TCIII increased significantly while TCII decreased. Vitamin B12 absorption was found to be impaired in 3 of 9 patients studied. There was no relationship seen between serum vitamin B12 level and vitamin B12 absorption. The mean values of serum folate and red cell folate levels in the patient group were significantly lower than those of normal subjects. Fifteen of 100 patients (15%) had serum folate level less than 3 ng/ml, while all of them had red cell folate higher than 100 ng/ml. Serum folic acid binding protein levels (FABP) in these patients, were not significantly different from those of normal subjects.

Vitamin B12 and vitamin B12 binding proteins in iron deficiency anaemia.

Vitamin B12 and vitamin B12 binding proteins were determined in 20 patients with iron deficiency anaemia who showed low haemoglobin, haematocrit, serum iron levels and hypochromic microcytic red blood cells. The serum vitamin B12 levels in these patients were significantly lower than that of the normal subjects. Nine of 20 patients had serum vitamin B12 less than 350 pg/ml. There was a significant increase in serum UBBC and TBBC levels in patient group and 9 of 20 patients had higher UBBC values than those of the normal subjects. The absolute values of TCI and TCII increased significantly while TCIII was within the normal limit even though the percentage of UBBC were not different from that of the normal subjects.