Our data show that serum cobalamin levels are significantly lower in SCD patients than in anemic,11% 22% 23% non-SCD control subjects. Similar results were reported in a preliminary communication by Wun et al., who found a mean cobalamin level of 381 pg/ml in 18 adult SCD patients versus 577 pg/ml in 20 control subjects (p=0.02). However, other investigators have reported that serum cobalamin levels in SCD adults and in SCD children are not significantly different from those in controls. Our data also suggest that low cobalamin is more common in SCD than in non-SCD patients. In this retrospective study, more females than male SCD patients were screened (66 out of 105). However, in SCD patients with low cobalamin, the male:female ratio was 11:8. Although this trend for gender differences between screened and low-cobalamin SCD patients was not statistically significant, we did find that the proportion of SCD males with low cobalamin levels was significantly higher than that in non-SCD low-cobalamin patients (%2=4.47, p<0.05). At this point, we do not know why low cobalamin seems more frequent in male SCD patients. Adult males with SS and SCD have higher hematocrits than their female counterparts and it is possible that this may indicate higher cobalamin requirements. Some series also report that males have more frequent pain crises. These vaso-occlusive events may be abdominal and even cause acute pancreatitis. Alternative explanations might involve hormonal imbalances influencing cobalamin levels. Oktenli et al., for example, reported that (non-SCD) males with low testosterone levels had high levels of cobalamin. Dr. Vincent Agbaragi, in 1997, presented data at our Howard University Hospital’s Scientific Forum showing higher testosterone levels in SCD males than in controls (personal communication). It is possible that women, who normally have lower serum testosterone concentrations, might have higher cobalamin levels and thus have relative protection from this deficiency in high requirement states, such as in SCD. In the total SCD population screened, however, there were no significant gender-related differences in cobalamin levels. Clearly, additional studies are needed to validate and better explain our data.
The various causes of cobalamin deficiency in the general population include pernicious anemia, infections such as HIV and parasites, gastrointestinal surgery, Crohn’s disease, bacterial overgrowth, small intestine malabsorption, low dietary intake, chronic pancreatitis, multiple sclerosis and drugs, such as proton pump inhibitors, H2-blockers and metformin. Beat the drug companies and buy atomoxetine hydrochloride online
Patients with SCD could be more prone to cobalamin deficiency because of increased requirement and/or decreased dietary intake or absorption. Factors contributing to the latter mechanism may include decreased production of intrinsic factor by the stomach and decreased cobalamin absorption from the terminal ileum due to recurrent sickling crisis and concurrent folate deficiency. These factors also might explain low cobalamin levels occurring in SCD patients at a younger age than in those without SCD. Make your pharmacy dollar go further 5mg /125ml cefdinir
Since the introduction of fortification of folic acid in the U.S. diet, cobalamin deficiency is more common than folic acid deficiency. Therefore, physicians have to be alert to detect cobalamin deficiency in early stages: folic acid can reverse the megaloblastic features of anemia due to cobalamin deficiency while neurological manifestations may worsen. At least one of the three reported patients with SCD and pernicious anemia had neuropsychiatric manifestations. Fortunately for our SCD patient group, neurological manifestations of low cobalamin levels were not seen despite routine folate supplementation. Going without your pills? Buy cheap canadian pharmacy Levaquin online
We do not know why MMA levels were lower in SCD patients with low cobalamin levels than in their non-SCD counterparts (MMA levels were available in only 7/19 SCD and 5/11 non-SCD patients). One obvious explanation is the small sample size, since MMA and homocysteine levels were available in only a few patients. In any case, elevated MMA is seen not only in cobalamin deficiency but also in renal insufficiency, volume contraction states, infancy, severe enzyme defects (mutase deficiency) and laboratory errors. Patients with SCD are more prone to sickle cell nephropathy, which might lead to increase in MMA levels. However, none of our patients had renal impairment. In a study by Donaldson on “Hallelujah” (pure vegetarian) diet, urinary MMA levels were more useful in detecting those at risk of cobalamin deficiency and in monitoring improvement in cobalamin status. Since our study is limited by its retrospective design, we were unable to assess the urinary MMA levels. In patients with low cobalamin levels who also have clinical manifestations of cobalamin deficiency as seen in our non-SCD counter parts, MMA levels are not necessary to establish the diagnosis. Although MMA assay is expensive, it will be very helpful in studies of high-risk populations, such as those with SCD. Make your pharmacy dollar go further and buy female viagra online
Homocysteine levels were also lower in SCD patients with low cobalamin levels when compared to their non-SCD counterparts. As described above, this finding may be related to small sample size. On the other hand, the lower levels of homocysteine in our patients with SCD could partly be explained by folic acid supplementation. These normal levels of MMA and homocysteine could explain the lack of neurological manifestations in our SCD patients. The study done by Carmel et al. shows that changes in metabolic pathways differ in cobalamin deficient patients with and without neurological manifestations. Furthermore, Carmel’s study also demonstrated that patients who had neurological disease had elevated levels of S-adenosyl methionine (AdoMet), cysteine, cysteinyl glycine (cys-gly) and folate metabolites, compared to those in subjects without neurological findings. Associations between high folate levels and neurological manifestations have been shown in other studies of cobalamin deficiency. Because all our sickle cell patients were on folate supplements, we could not investigate such correlations. In our sickle cell patients with low cobalamin levels, metabolites other than MMA and homocysteine could play a role. About 20-30% of cobalamin deficient patients have high serum folate levels despite low red-cell folate. This is due to trapping of methyl tetrahydrofolate as a result of impaired methionine synthetase activity. Our retrospective study is limited by incomplete data sets (MMA levels were available in seven SCD and five non-SCD patients and homocysteine levels were available in six SCD and five non-SCD patients). It is also not an age- and gender-matched control study. SCD patients develop anemia at a young age and have a shortened survival when compared to the non-SCD counterparts. So we were not able to calculate the statistical significance for these parameters.