Pseudodementia in a twenty-one-year-old with bipolar disorder and vitamin B12 and folate deficiency

A twenty-one-year-old female known to suffer from bipolar type 1 disorder developed features of a pseudodementia. Following prompt initial response to treatment with antidepressants, there was an early recurrence of cognitive impairment. Blood investigations confirmed a macrocytic anaemia and vitamin B12 and folate deficiencies. There was dramatic resolution of cognitive impairment after vitamin replacement. This suggested the occurence of a reversible nutritional dementia and reinforced the need to rule out secondary organic causes of psychiatric symptoms even in patients previously diagnosed with a primary psychiatric disorder.(Au)

Neural tube defects in Jamaica following Hurricane Gilbert

An increased incidence of obvious live-birth neural tube defects (i.e., spina bifida cystica and encephalocele) occurred in Jamaica 11 to 18 months after Hurricane Gilbert. The conceptions of the affected babies coincided with a rise in megaloblastic change in sickle cell patients, suggesting a wide-spread drop in dietary folate intake. A detailed history was taken from each of the 17 affected mothers (case subjects) and 51 unaffected mothers (matched control subjects). The case subjects reported a significantly lower mean intake of dietary folate in the periconceptional period (154 micograms/day) than did the control subjects (254 micrograms/day). The temporary increase in neural tube defects was associated with a dietary level of folate that fails to protect against neural tube defects under natural conditions. (AU)

Treatment of sickle cell disease in early childhood in Jamaica

The Jamaican sickle cell cohort study, based on neonatal diagnosis of all cases of sickle cell disease among 100 000 consecutive births, has identified acute splenic sequestration (ASS) and pneumoccocal disease as the most important complications in early life. The etiology of ASS is unknown and prophylaxis is therefore not possible. For first attacks, attention has been directed to parental education to achieve earlier diagnosis. Recurrent attacks may be prevented by prophylactic splenectomy. A controlled trial on the prevention of pneumococcal disease has indicated many pneumococcal septicemias in children given the 14 valent pneumococcal vaccine between the ages of 6 months and 3 years. No pneumococcal isolations occurred during the same period in children given monthly long-acting prophylactic penicillin. A controlled trial of foliate supplementation for 1 year in children aged 6 months to 4 years indicated no difference between control and treatment groups in hemoglobin levels or weight and height velocity. The MVC was 4 fl less in the supplemented group. A controlled trial of feeder vessel photocoagulation in the therapy of proliferative retionpathy indicated significantly less vitreous hemorrhage in treated patients but choroidal neovascularization was a common complication of xenon arc therapy and retinal tears commonly followed the use of Argon laser. A new trial of scatter therapy is in progress. (AU)

A trial of folate supplementation in children with homozygous sickle cell disease

A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented groups showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of datylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed (AU)

Haematological levels in Jamaican infants

A longitudinal study of 300 infants from birth to 1 year of age was carried out in Kingston, Jamaica. Haemoglobin levels were estimated 7 times during the year and serum iron and total iron binding capacity once. Hb electrophoresis was performed. In singleton children with Hb genotype AA, AS, or AC, and of birthweight 2.5kg or over, Hb levels were low after 3 months of age. These low levels were associated with iron deficiency, which was probably due to poor iron stores at birth followed by poor iron intake or absorption. It was not possible to determine whether folic acid deficiency or protein deficiency was also important. Hb levels varied with age, socioeconomic class, birthweight, sex, and rate of weight gain. The growth and health of 4 girls with homozygous sickle cell disease is mentioned.(AU)

Haemoglobin, iron, folate and vitamin B12 levels in pregnant and lactating women in Jamaica

An island-wide survey of 167 unselected pregnant or lactating Jamaican women revealed a 45 per cent incidence of iron deficiency anaemia during pregnancy and the first six months of lactation. A high incidence of eosinophilia, probably the result of intestinal parasitism, was noted. There was no evidence that folate deficiency contributed to the anaemia in these women although red cell folate levels fell throughout pregnancy and the first six months of lactation. Two women who had uncomplicated folate deficiency were not anaemic. Serum B12 levels were found to be considerably higher than those reported in European women during pregnancy and lactation and the lower levels were found in the second rather than the third trimester (AU)

Folic acid and vitamin B12 studies in megaloblastic anaemia of infancy (abstract only)

The clinical and haematological features of megaloblastic anaemia of infants are briefly reviewed. The results of assays of urinary formiminoglutamic acid on 12 infants are presented. Folic acid is required for the normal degradation of formiminoglutamic to glutamic acid and consequently in folic acid deficiency elevated levels of formiminoglutamic acid are found. The results indicate clearly that the disease is due to a deficiency of folic acid, and this is confirmed by the demonstration of normal vitamin B12 levels in the six infants in whom this assay was performed (AU)

Sickle-cell anaemia complicated by megaloblastic anaemia in infancy

In a series of fifty cases of megaloblastic anaemia of infancy five cases with associated sickle-cell anaemia were seen. These cases presented with unusually low haemoglobin and reticulocyte levels for sickle-cell anaemia, and the bone marrows were megaloblastic. Folic-acid therapy produced a dramatic increase in reticulocytes and a raise in haemoglobin to the level normally seen in sickle-cell anaemia. Some degree of associated iron deficiency was present in all cases. In one of the cases described it was possible to measure the half-life of transfused erythrocytes with reasonable accuracy. The cell survival was found to be normal. The question of crisis in sickle-cell anaemia is discussed (Summary)

Megaloblastic anaemia of infancy in Jamaica

The terms "megaloblast" and "megaloblastic anaemia" are defined. The megaloblast is a pathological cell and it is only found, specifically, in anaemias which are attributable to a deficiency of certain essential haemopoietic factors present in liver. The morphology of normoblasts and of megaloblasts, i.e. a cell with some of the characteristics of both a megaloblast and a normoblast, is discussed. The charateristic changes in the granulocytic series of cells, which are seen in megaloblastic anaemias, are discussed. The development of knowledge with regard to the essential haemopoietic factors present in liver is described, and the possible roles, and interrelationships of folic acid, folinic acid and vitamin B12 are discussed. It is concluded that, although their precise functions are still uncertain, there is no doubt as to their importance in nucleic acid synthesis. The literature on megaloblastic anaemia of infancy is reviewed. The rather rare association between infantile malnutrition and megaloblastic anaemia are discussed, and the fact that anaemia of any severe degree is unusual in kwashiorkor is stressed. The few available bone-marrow studies in kwashiorkor are described. A megaloblastic bone marrow has not very commonly been seen in kwashiorkor except in Durban, South Africa. A condition which resembles kwashiorkor very closely has been reported from Sicily. These infants are often very anaemic and a megaloblastic bone marrow is commonly seen. The clinical, haematological and other laboratory findings on fifty cases of megaloblastic anaemia of infancy are presented. From the clinical point of view the most striking feature was that all the infants were very malnourished and grossly under-weight. On haematological examination the best valuable finding from a diagnostic point of view was found to be the haemoglobin level. If this is below 7.0 g percent the anaemia is almost certainly going to be megaloblastic. A full blood count with determination of mean corpuscular volume, and haemoglobin concentration is rarely helpful since the anaemia is usually normocytic and normochronic. A certain diagnosis can be made by bone marrow puncture. Of the 50 cases, 45 were tested with folic acid, and 5 received vitamin B12. Six of the folic acid treated cases died. In the 39 folic acid treated who recovered, the haematological and clinical response was excellent. The 5 cases treated with vitamin B12 also showed a good haemotological and clinical response, although the dosage used was large. The majority of cases received antibiotics, and some received several, but in no case was a haematological response observed. The morphology of the bone marrow in haemaloblastic anaemia of infancy is described and extensively illustrated. In addition to typical megaloblasts, erythroblasts of intermediate type were commonly observed. The characteristic white cell abnormalities are also described. Changes in the nuclear chromatin structure of the megakaryocytes were also noted, which resemble the changes seen in megaloblasts quite closely. The post-mortem findings in the six fetal cases are summarized. Extramedullary erythropoiesis was observed in the livers of three cases, and in two a severe chronic fatty change was presented. In one case an acute fatty change was seen. The results of liver biopsies carried out on twelve other infants are also reported. Extra-medullary erythropoiesis was found in seven out of the ten specimens which were sectioned histologically. This finding of extra-medullary erythropoiesis is regarded as being pathognomonic of the disease, although it is not invariably present. Five cases of sickle cell anaemia with associated megaloblastic anaemia are described. This association has only been reported once before in infancy. Three other instances are recorded in the literature in older children. The association is highly significant, since a total of five cases out of fifty exceeds the expected incidence by no less than 3 times. An unexpected and unexplained finding was that three of these cases were also demonstrably iron deficient. The pathogenesis of the disease is considered in detail. It is thought that dietary deficiency is the most important factor, but whether of folic acid or vitamin B12 is uncertain. A deficiency of folic acid seems more likely. The possible significance of ascorbic acid deficiency in the aetiology of the disease is discussed, and the literature on the experimental production of megaloblastic anaemia in monkeys by means of a diet low in folic acid and deficient in ascorbic acid is reviewed. Only one infant in the present series had frank scurvy, and in this case ascorbic acid was required in addition to folic acid to produce a satisfactory haematological and clinical response. The importance of infection in the causation of the disease is discussed. Infections of various types were extremely common especially upper respiratory infections and gastro-enteritis. The role of gastro-enteritis is illustrated by six case in which specific pathogens were isolated from the stools. The possible mechanisms, which may be of importance in the causation of the disease, are listed: (1) A dietary deficiency of haemopoietic substance is thought to be the most significant factor. (2) An intrinsic factor deficiency is suggested speculatively as possibly playing a part. (3) Impaired absorption of haemopoietic factors due to diarrhoea is undoubtedly important. (4) Excessive utilization of haemopoietic factors by an abnormal bacterial flora in the intestine may contribute to a deficiency. (5) Diminished synthesis of haemopoietic factors by an abnormal bacterial flora in the intestine may also play a part. In conclusion some possible lines of future investigation of the disease are discussed (Summary)

The biochemical evaluation of the folacin (folic acid, pteroylmo-glutamic acid, folate) nutrition status

Measurement of folate levels in serum and red blood cells is the most practical procedure to evaluate folacin nutritional status in population groups and clinical patients. Subjects with a suspected folacin deficiency should, however, be evaluated further to eliminate the possibility of pernicious anemia or a dietary vitamin B12 deficiency. Serum vitamin B12 analyses can be useful for this purpose. If facilities are available, FIGLU tests can provide additional diagnostic information in clinical situations (AU)