Search

Cerebral folate deficiency (CFD) results in neurological alterations and a massive degeneration of the choroid/retina if left untreated, which limit the visual field and visual acuity. This article reports the case of a female patient with CFD, who developed autistic personal characteristics prior to reaching school age and first started to speak at the age of 3 years. At the age of 6 years she was presented because of unclear reduced visual acuity in the right eye. At that time mild bilateral peripheral chorioretinal atrophy was present, which subsequently became more pronounced. Additionally, a centrally emphasized chorioretinal atrophy further developed. Visual acuity of both eyes progressively deteriorated until stagnating at 0.1 at the age of 14 years. The causal assignment of the findings of the patient was not possible for many years. Choroideremia was excluded by molecular genetic testing (CHM gene with no mutations) and gyrate atrophy was ruled out by a normal ornithine level. The existence of a mitochondrial disease was almost completely excluded by exome sequencing. After the onset of further nonocular symptoms, e.g. neuromuscular disorders, electroencephalograph (EEG) alterations and autistic disorder, intensified laboratory diagnostics were performed in the treating pediatric hospital. Finally, an extremely low level of the folic acid metabolite 5‑methyltetrahydrofolate was detected in the cerebrospinal fluid (CSF) leading to the diagnosis of CFD. High-dose substitution treatment with folic acid was subsequently initiated. After excluding the presence of a pathogenic mutation of the FOLR1 gene for the cerebral folate receptor 1, a high titer blocking autoantibody against cerebral folate receptor 1 was detected as the cause.

We performed a systematic literature search for diagnostic criteria in establishing cobalamin deficiency. The diagnostic procedure is particularly uncertain in elderly patients with neurological symptoms and in cases with borderline cobalamin values. In any patient with suspected cobalamin deficiency we recommend analysing a full blood count and determining cobalamin concentration in a serum sample. Particularly in elderly patients and cases with neurological symptoms presenting borderline cobalamin values and no abnormalities in the blood count, we recommend further investigation with methylmalonic acid, homocystein and Schilling test. These additional tests should make it possible to decide whether to recommend lifelong substitution with cobalamin. Various cobalamin assays, Schilling test, food cobalamin test, gastroscopic evaluation and the problems surrounding these assays in the elderly are discussed. Our own experience with methylmalonic acid, homocystein determination and food cobalamin test did not reveal a simple diagnostic procedure in such cases. We conclude that there is still no "gold standard" for diagnostic procedure in the special cases mentioned.

After discussing the problem of folic acid requirements and supply during pregnancy, the results of a longitudinal study on 162 pregnant women are presented. By measuring biochemical and morphological changes in two subgroups (non-substituted vs unspecifically substituted), the necessity of a substitution with folic acid is discussed, as there might be additional requirements for the pregnant and the foetal organism. Concentrations of folic acid in the maternal plasma and in the erythrocytes as well as the segmentation rate and hypersegmentation of the granulocytes show a clear decrease in pregnancy. At the same time there was a significant difference between the subjects substituted and not substituted; the foetus and newborn levels were much higher than their mothers' concentrations. Moreover, there was a correlation between red cells folic acid levels in the last trimester and duration and outcome of pregnancy. These results indicate a substitution with folic acid for certain populations in pregnancy, which are highlighted.

Because of anaemia and dystrophy a girl was admitted to hospital. By bone marrow aspiration the diagnosis of a megalocytic anaemia was established. The determination of folic acid revealed a severe folate deficiency caused by education problems with consecutive malnutrition. Under folic acid replacement therapy and intensive talks with the parents the girl recovered from her illness and after change of nutrition she developed well without any further folic acid replacement.

Criteria to judge the folate supply have been evaluated in previous studies. The present study is examining parameters to estimate the degree of folate deficiency. Serum folate levels and erythrocyte folate concentrations were measured in 116 volunteers (patients). The erythrocyte folate is to a large extend independent of exterior supply and is lowered only in severe chronic deficiency. Low levels of erythrocyte folate indicate longstanding undersupply. Our experiments show that folate concentration of greater than 250 ng per ml erythrocytes indicate adequate supply. Concentrations below this limit are characteristic for chronic folate deficiency. To confirm this statement further studies will take into account the urine concentration of formiminoglutamic acid.

Folic acid concentration in serum and erythrocytes was measured by radio assay according to the principle of competitive binding to proteins with 125I as marker. The method yielded a linear regression with readily reproducible results. The mean value in controls was 7.05 -+/ 3.4 ng/ml in serum and 386.8 -+/ 215.1 ng/ml in erythrocytes. In chronic alcoholics the respective values were significantly lower: 4.79 -+/ 2.02 ng/ml for serum and 344.4 -+/ 198.9 ng/ml for erythrocytes. The clinical importance of folic acid estimations arises from the general frequency of folic aicd deficits. Latent folic acid deficiency is associated with lowered folic acid concentrations in serum and normal values in red cells. In manifest folic acid deficiency both concentrations are decreased.

A review of published research data on the requirement, intake, and signs of deficiency of vitamins and trace elements in old age is presented. It particularly deals with the problem of a general indication for vitamins and trace element supplements - the mean components of geriatric preparations. Special emphasis is laid on the question if these substances exhibit a specific effect on the alterations of physical and psychic capacity typically accompanying the growing old. It could be shown that in several groups of the elderly diminished vitamin levels are common and/or vitamin and trace element intake does not reach daily recommended allowances. But it still remains unclear if these findings have to be considered as disease symptoms.

In a study on 130 student volunteers the segmentation of neutrophil granulocytes was measured. The serum folate concentration was used as biochemical reference. Both parameters indicate the state of folate supply or the degree of folate deficiency, respectively. Considering the haematologic response as an objective criterion only 71% of the examines showed an adequate folate status. 11% were found "deficient" and 18% were in a marginal state of folate supply. This result was confirmed by repeating the experiment. Further studies are to include folate concentration of erythrocytes and urine concentration of formiminoglutamic acid.

After presentation of morphological and clinical characteristics concerning megaloblastic anemias, the differential diagnostic possibilities of these anemia, ase discussed. Finally a short survey concerning the therapeutic procedure is presented.