vitamin-b-12 and Failure-to-Thrive

Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

Topics: Adult; Anemia, Pernicious; Brain; Developmental Disabilities; Diet, Vegetarian; Failure to Thrive; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Mothers; Nervous System Diseases; Pregnancy; Psychomotor Disorders; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Adult; Anemia, Pernicious; Breast Feeding; Developing Countries; Diet, Vegetarian; Failure to Thrive; Female; Humans; Infant; Infant Food; Infant Welfare; Lactation; Milk, Human; Nutrition Policy; Vitamin B 12; Vitamin B 12 Deficiency

A male Caucasian infant presented at 6 weeks of age with failure to thrive, diarrhoea, macrocytic anaemia, and decreased IgG. He had normal serum B12 and folate levels. Serum cobalamin binding capacity showed no detectable transcobalamin II. Both parents showed levels consistent with a heterozygous state. The literature is extensively reviewed, and the importance of early diagnosis to prevent neurological dysfunction is stressed.

Topics: Failure to Thrive; Humans; Infant; Male; Transcobalamins; Vitamin B 12

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Topics: Anemia, Megaloblastic; Bone Marrow; Diagnosis, Differential; Early Diagnosis; Early Medical Intervention; Failure to Thrive; Folic Acid; Folic Acid Deficiency; Humans; Infant; Male; Pancytopenia; Prenatal Care; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Transcobalamin II deficiency is one of the rare causes of inherited vitamin B12 disorders in which the patients have characteristically normal or high vitamin B12 levels related to the transport defect of vitamin B12 into the cell, ending up with intracellular cobalamin depletion and high homocysteine and methylmalonic acid levels.. Herein, we describe the findings at presentation of four patients who were diagnosed to have transcobalamin II deficiency with novel mutations.. These patients with transcobalamin II deficiency were found to have novel mutations, of whom 2 had the same large deletion (homozygous c.1106+1516-1222+1231del).. Transcobalamin II deficiency should be considered in differential diagnosis of any infant with pancytopenia, failure to thrive, diarrhea, and vomiting.. Amaç: Transkobalamin II eksikliği nadir bir kalıtsal B12 vitamini bozukluğudur. Defektin B12 vitamininin transportu ile ilgili olması nedeniyle hastalar normal ya da yüksek B12 vitamini düzeylerine eşlik eden yüksek homosistein ve metilmalonik asit düzeylerine sahiptir. Gereç ve Yöntemler: Bu çalışmada transkobalamin II eksikliği tanısı alan dört hasta sunulmuştur. Bu hastalarda daha önce bildirilmemiş yeni mutasyonlar saptanmıştır. Bulgular: Hastaların ikisinde aynı büyük delesyon olduğu görülmüştür (homozigot c.1106+1516-1222+1231del). Sonuç: Pansitopeni, büyüme geriliği, ishal ya da kusması olan tüm bebeklerde transcobalamin II eksikliği ayırıcı tanıda düşünülmelidir.

Topics: Anemia, Megaloblastic; beta-Thalassemia; Bone Marrow; Chromosomes, Human, Pair 22; Codon, Nonsense; Consanguinity; Failure to Thrive; Female; Folic Acid; Frameshift Mutation; Genotype; Humans; Hydroxocobalamin; Infant; Male; Mutation; Mutation, Missense; Pancytopenia; Sequence Deletion; Transcobalamins; Vitamin B 12; Vomiting

Vitamin B12 deficiency is rare in children, with nonspecific symptoms including failure to thrive, vomiting, anorexia, and neurologic changes with or without hematologic disturbances. The neuropathy can be severe and irreversible. We report four cases of children with B12 deficiency secondary to adult type pernicious anemia, a presumed transport protein abnormality, and a metabolic defect. All demonstrated neurologic compromise that improved after initiation of B12 therapy. Hematologic manifestations may be preceded by constitutional, gastrointestinal, or neurologic changes, and must raise concern for B12 deficiency. Therapy should be initiated promptly in this setting to prevent irreversible neuropathy.

Topics: Adolescent; Adult; Anemia, Pernicious; Child, Preschool; Failure to Thrive; Female; Humans; Male; Prognosis; Vitamin B 12; Vitamin B 12 Deficiency

A 14 year male adolescent born of 2nd degree consanguineous marriage presented with asymptomatic proteinuria and severe anemia. He had leucopenia, anisopoikilocytosis, megaloblastic erythropoiesis, megakaryocytes with low serum B12 level. His younger sibling was similarly affected. This combination suggested Imerslund-Grasbeck syndrome. The hemoglobin levels improved with injection of vitamin B12 but proteinuria persisted. During follow-up, he developed ketoacidosis due to insulin dependent diabetes mellitus. This rare combination has not been reported in the Indian literature.

Topics: Adolescent; Anemia, Megaloblastic; Child; Diabetes Mellitus, Type 1; Failure to Thrive; Humans; Hyperpigmentation; Intestinal Absorption; Malabsorption Syndromes; Male; Mutation, Missense; Prevalence; Risk Factors; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Weight loss and reduction of motor skills resulted in paediatric evaluation of a 10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and delayed development due to vitamin B12 deficiency caused by strict maternal vegan diet during pregnancy and nursing. Therapy with cyanocobalamin was instituted with remission of symptoms. Since infants risk irreversible neurologic damage following severe vitamin B12 deficiency, early diagnosis and treatment are mandatory. Vegan and vegetarian women should take vitamin B12 supplementation during the pregnancy and nursing period.

Topics: Breast Feeding; Diet, Vegetarian; Failure to Thrive; Female; Humans; Infant; Male; Milk, Human; Mothers; Pregnancy; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.

Topics: Breast Feeding; Developmental Disabilities; Diet, Vegetarian; Failure to Thrive; Humans; Infant; Male; Movement Disorders; Vitamin B 12; Vitamin B 12 Deficiency

It is unusual for inborn errors of metabolism to be considered in the investigative work-up of pancytopenia. We report a family in which the proband presented with failure to thrive at 2 months of age and subsequent bone marrow failure. A previous sibling had died at 7 months of age with suspected leukaemia. Haematological findings in the proband were significant for pancytopenia, and bone marrow aspiration showed dysplastic changes in all cell lineages. Urinary organic acid analysis revealed elevated methylmalonic acid. The synthesis of transcobalamin II (transcobalamin, TC) by cultured fibroblasts was markedly reduced, confirming the diagnosis of TC deficiency. The proband and his younger asymptomatic sister (also found to have TC deficiency) were homozygous for R399X (c.1195C>T), a novel mutation resulting in the loss of the C- terminal 29 amino acids of TC, a highly conserved region. Response to parenteral vitamin B(12) in the proband was dramatic. At 6 years 3 months of age, physical examination is normal and developmental level is age appropriate. His sister is clinically asymptomatic and is also developing normally. Propionylcarnitine concentrations were not elevated in the newborn screening cards from the proband and sister, but that was for specimens retrieved from storage after 7 years and 5 years, respectively. Inherited and acquired cobalamin disorders should both be considered in the differential diagnosis of bone marrow failure syndromes in young children. Early detection of the metabolic causes of bone marrow failure can ensure prompt recovery in some cases involving the vitamin B(12) pathway.

Topics: Biomarkers; Bone Marrow Diseases; Bone Marrow Examination; Cells, Cultured; Child; Child Development; Child, Preschool; DNA Mutational Analysis; Failure to Thrive; Female; Fibroblasts; Genetic Predisposition to Disease; Humans; Infant; Male; Metabolism, Inborn Errors; Mutation; Pancytopenia; Pedigree; Phenotype; Transcobalamins; Treatment Outcome; Vitamin B 12

The newborn's vitamin B12 storage exclusively comes from placenta transfer, later from animal food. We relate 3 observations of infants (3-11-13 months) with failure to thrive, anorexia, vomiting and for the two olders refusal of weaning, associated with psychomotricity regression and hypotony. Blood cell count showed a macrocytosis without anemia (case 2-3) and a severe microcytic anemia for the first case caused by a mild alpha-thalassemia, with megaloblastic bone marrow. Vitamin B12 levels were very low associated with increased methylmalonic acid and homocysteine serum levels which confirm the diagnostic . Cerebral imaging showed diffuse cortical atrophy. Cobalamin deficiency was caused by strict vegetarian diets mothers of breastfed infants (cases 2-3) and for younger by mother's unrecognized pernicious anemia. 3 mothers had no anemia and normal B12 's levels at diagnosis. Vitamin B12 supply lead to a rapid clinical and hematologic improvement. In two cases, neurologic recovery was incomplete. About one hundred case of B12 deficiency 's infant are reported, 2/3 are breast-fed by vegetarian mothers, and 1/4 have mothers with pernicious anemia. The failure to thrive is due to anorexia, refusal of weaning and partial villous atrophy. Neurologic manifestations are secondary to cerebral disorders, sometimes revealed by an exposure to anesthetic nitrous oxyd. The macrocytic anemia is inconstant. The etiologic research of developmental delay in an infant may include vitamin B12's deficiency, even if there is no haematologic signs, especially if breast-fedding 's mothers is vegetarian.

Topics: Atrophy; Brain; Failure to Thrive; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Psychomotor Disorders; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Vomiting

We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.

Topics: Anemia, Megaloblastic; Bone Marrow Examination; Diagnosis, Differential; Diet, Vegetarian; Failure to Thrive; Female; Follow-Up Studies; Humans; Hydroxocobalamin; Infant; Injections, Intravenous; Pregnancy; Pregnancy Complications; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Two infant boys of 7 and 12 months respectively who presented with symptoms of failure to thrive and developmental delay were diagnosed with vitamin B12 deficiency. This deficiency is a rare condition in infants living in developed countries. It does occur, however, in infants who are breastfed by mothers with an inadequate diet. Both of the children studied were breastfed by vegetarian mothers. Following vitamin suppletion, both children showed signs of recovery. The importance of considering vitamin deficiencies in similar infants presenting with failure to thrive is emphasized. Moreover, maternal dietary habits in breastfed children should be checked. To prevent irreversible neurological damage, early recognition of any nutritional deficiencies is important.

Topics: Adult; Breast Feeding; Developmental Disabilities; Failure to Thrive; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Male; Maternal Nutritional Physiological Phenomena; Milk, Human; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Breast Feeding; Diet, Vegetarian; Failure to Thrive; Humans; Infant; Infant Nutritional Physiological Phenomena; Male; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D

The Imerslund-Gräsbeck syndrome (IGS) is a rare inherited disorder characterized by a megaloblastic anemia due to a selective vitamin B12 malabsorption in association with a mild proteinuria. Usually recurrent infections, gastrointestinal complaints, and pallor are presenting symptoms. We report two cases of IGS with an unusual presentation.. Two girls are described with the Imerslund-Gräsbeck syndrome who had a failure to thrive as a presenting symptom without infections or gastrointestinal complaints. The diagnosis of IGS was based on marked macrocytic anemia, very low serum vitamin B12 levels, abnormal Schilling urinary excretion test results, and mild proteinuria. When parenteral vitamin B12 was started, a rapid catch-up growth was seen in both girls.. The absence of well-known causes of failure to thrive, such as recurrent infections and gastrointestinal complaints, favors the concept that the metabolic disturbances caused by an isolated cobalamin deficiency as seen in IGS causes a failure to thrive.

Topics: Anemia, Megaloblastic; Failure to Thrive; Female; Humans; Infant; Proteinuria; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

A 9-month-old sexually intact male longhair cat was examined because of lethargy, anorexia, cold intolerance, and failure to thrive since acquisition at an early age. Clinical signs of disease were less pronounced when the cat was fed a low-protein diet. Anemia, hypoglycemia, low total CO2 content, and hyperammonemia were detected. The cat was euthanatized. Urine obtained immediately before euthanasia contained a large amount of methylmalonic acid. Total serum cobalamin concentration was low. Hepatic methylmalonic-CoA mutase activity, with and without the addition of coenzyme adenosylcobalamin, was consistent with a cobalamin deficiency. Methylmalonic acidemia secondary to a putative defect in cobalamin absorption was diagnosed.

Topics: Absorption; Amino Acid Metabolism, Inborn Errors; Amino Acids; Animals; Cat Diseases; Cats; Dietary Proteins; Failure to Thrive; Liver; Male; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Sleep Stages; Vitamin B 12; Vitamin B 12 Deficiency

In a group of nine children with postenteritis enteropathy (i.e., persisting small-intestinal mucosal damage and failure-to-thrive after an acute episode of gastroenteritis), absorption capacities for vitamin B12 and folic acid were studied and compared with hematological status in peripheral blood. The fractional absorptions of vitamin B12 (FAB12) and folic acid (FAFol) were determined by means of a double-isotope technique employing a single-stool-sample test. The children were examined when growth retardation was maximal, and examinations were repeated during the late recovery period. In spite of considerable small-intestinal mucosal damage, only the absorption of vitamin B12 was markedly affected, while that of folic acid was almost intact. When growth retardation was maximal, FAB12 was below the normal age-correlated range in half of the children. FAB12 was also severely reduced in all longitudinally observed children when compared with the results obtained during the late recovery period (p less than 0.005). FAFol was below the normal range in one fourth of the children, but the reduction was modest and insignificant when compared with the results of repeated examinations during the late recovery period. A moderate iron deficiency was detected in half the children. High levels of plasma vitamin B12, folic acid, and erythrocyte folate were detected at both early and later examinations, indicating that these parameters were not affected by the reduced absorption capacities. However, if malabsorption and chronic diarrhea are combined with low dietary intake of vitamin B12, as is the case for many children in the Third World, depletion of vitamin B12 stores may result.

Topics: Absorption; Diarrhea; Erythrocyte Indices; Failure to Thrive; Female; Folic Acid; Gastroenteritis; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Vitamin B 12

An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life-threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co-cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood.

Topics: Failure to Thrive; Female; Homocystinuria; Humans; Infant; Intestinal Absorption; Malonates; Methylmalonic Acid; Pancytopenia; Transcobalamins; Vitamin B 12

A 7-month-old male presented with lethargy and failure to thrive. The child was exclusively breast-fed from birth by a mother who was a strict vegetarian. Laboratory data revealed macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The patient responded well to supplementation with B12 alone and was developmentally normal by 11 months of age. This study emphasizes the need for assuring maternal dietary adequacy during pregnancy and after birth.

Topics: Adult; Body Height; Body Weight; Breast Feeding; Diet, Vegetarian; Failure to Thrive; Female; Humans; Infant; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Child; Corrinoids; Failure to Thrive; Feeding and Eating Disorders; Growth; Humans; Infant; Physiological Phenomena; Secologanin Tryptamine Alkaloids; Thiamine; Vitamin B 12

Topics: Child; Dietary Supplements; Failure to Thrive; Growth; Humans; Infant; Thiamine; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Corrinoids; Dietary Supplements; Failure to Thrive; Growth; Humans; Vitamin B 12; Vitamin B Complex