Solid food refusal as the presenting sign of vitamin B<Subscript>12</Subscript> deficiency in a breastfed infant

Dietary vitamin B₁₂ (vitB₁₂) deficiency, although common in the elderly, is rare in childhood. We report on an exclusively breastfed 8-month-old infant, presenting with persistent refusal of solid foods. Three months later, developmental regression and failure to thrive led to the diagnosis of vitB₁₂ deficiency, as a consequence of a subclinical pernicious anaemia with vitB₁₂ deficiency in the mother. Treating the infant with parenteral vitB₁₂ induced prompt recovery including acceptance of weaning food. Conclusion: This case illustrates refusal of complementary foods as a presenting symptom of vitB₁₂ deficiency in a breastfed infant. Symptoms, diagnostic tests and treatment of vitamin B₁₂ deficiency are reviewed. Early diagnosis and treatment are important to prevent irreversible neurological damage.     

Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature

Vitamin B₁₂ deficiency is one of the major causes of megaloblastic anaemia with or without neurological symptoms. We report on a patient manifesting acute encephalopathy, epilepsy, microcephaly and megaloblastic anaemia at the age of 4 months. Vitamin B₁₂ deficiency in the patient was due to subclinical pernicious anaemia of the mother who exhibited neither haematological nor neurological symptoms. Mother and child both had elevated methylmalonic acid in their urine which is a sensitive parameter of vitamin B₁₂ deficiency. Vitamin B₁₂ therapy resulted in arrest of convulsions within 24 h. There were no further seizures although the patient showed moderate mental retardation at the age of 7 years but a normal head circumference. Long-term MRI follow-up, performed at the age of 7 years, showed moderate enlargement of the ventricles with reduction of myelin and hypoplasia of the corpus callosum. Conclusion:vitamin B₁₂ deficiency due to maternal pernicious anaemia should always be considered in the differential diagnosis of neurological symptoms in infants and especially in combination with megaloblastic anaemia. Since the age of onset and the duration of neurological symptoms may contribute to the development of long-term symptoms, early diagnosis and treatment is important for vitamin B₁₂ deficient children.     

Severe vitamin B12 deficiency in an infant associated with a maternal deficiency and a strict vegetarian diet

The authors present a case of severe megaloblastic anemia and neurologic damage due to vitamin B12 deficiency in a 6-month-old infant. The cause of the vitamin deficiency was a maternal dietary deficiency because of a strict vegetarian diet and prolonged breast-feeding. The importance of early recognition of significant maternal vitamin B12 deficiency during pregnancy and lactation in vegetarians is emphasized so that appropriate supplementation can be given and irreversible neurologic damage in the infant prevented.     

Vitamin B12 deficiency in a 9-month-old boy

We present a 9-month-old boy with megaloblastic anaemia, neutropenia and hypogammaglobulinaemia due to vitamin B12 deficiency. The deficiency was secondary to prolonged exclusive breastfeeding with inadequate nutritional amounts of vitamin B12 from the mother. There were no clinical or biological signs of maternal anaemia or macrocytosis. Treatment with oral vitamin B12 rapidly improved the biological findings of the child. Vitamin B12 deficiency should be considered in infants older than 2 months presenting with failure to thrive, neurocognitive retardation or even pancytopenia and hypogammaglobulinaemia, even in the absence of any signs of maternal anaemia or macrocytosis. Therefore, evaluation of vitamin B12 status during pregnancy and lactation is necessary in order to prevent B12 deficiency and its possible long-term effects in infants. Conclusion: Further studies should be conducted to evaluate the optimal oral dosage of vitamin B12 in children since limited data on the use of oral B12 substitution are available.     

Failure to thrive and psychomotor regression revealing vitamin B12 deficiency in 3 infants]

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.     

PANCYTOPENIA DUE TO VITAMIN B12 DEFICIENCY IN A BREAST-FED INFANT

Nutritional B12 deficiency in childhood is an uncommon disorder. Most cases are due to maternal insufficiency, resulting from deficient stores and intake, and is generally seen in exclusively breast fed infants. This report describes a breast-fed infant with megaloblastic anemia secondary to maternal vitamin B12 deficiency. We describe this patient to remind readers that B12 deficiency may cause severe pancytopenia and regression of motor functions. These patients can present with unexpected signs and symptoms, such as developmental delay and regression as in our patient. It is also important to take the nutritional history of both the child and the mother of early prevention and treatment. With early awareness and appropriate measures potentially irreversible neurologic damage can be prevented in the infant.     

Pancytopenia due to vitamin B12 deficiency in a breast-fed infant

Nutritional B12 deficiency in childhood is an uncommon disorder. Most cases are due to maternal insufficiency, resulting from deficient stores and intake, and is generally seen in exclusively breast fed infants. This report describes a breast-fed infant with megaloblastic anemia secondary to maternal vitamin B12 deficiency. We describe this patient to remind readers that B12 deficiency may cause severe pancytopenia and regression of motor functions. These patients can present with unexpected signs and symptoms, such as developmental delay and regression as in our patient. It is also important to take the nutritional history of both the child and the mother of early prevention and treatment. With early awareness and appropriate measures potentially irreversible neurologic damage can be prevented in the infant.     

Hereditary juvenile cobalamin deficiency due to mutations in GIF gene

Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia due to cobalamin deficiency, results from defects in Cbl absorption. There is a lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption of vitamin B12 or Imerslund-Gr?sbeck syndrome. Differential diagnosis can't be accomplished only by clinical and biochemical findings. We present a patient from Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The patient is a compound heterozygous in GIF gene for a splice site mutation inherited from his mother and a missense change inherited from his father. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions.     

Developmental regression as an early manifestation of vitamin B12 deficiency

Loss of previously attained developmental milestones in an infant is often associated with central nervous system tumor, neuromuscular disease, or an inborn metabolic error. An infant with developmental regression and involuntary movements who was found to be vitamin B12 deficient on the basis of unrecognized maternal vitamin B12 deficiency is described. The infant had a dramatic neurologic recovery after receiving vitamin B12. The case and a review of similar cases is presented.     

Nutritional Vitamin B12 Deficiency in a Breastfed Infant Following Maternal Gastric Bypass

Breasfed infants of women who have had gastric or intestinal bypass procedures may develop nutritional deficiencies. We describe a 10-month-old exclusively breastfed white male infant who presented with vomiting, failure to thrive, and megaloblastic anemia. He was found to have vitamin B₁₂ deficiency. His mother had undergone a gastric bypass procedure for morbid obesity 2 years Prior to her pregnancy with this child. She had subclinical vitamin B₁₂ deficiency, with an abnormal Schilling test that corrected with the addition of intrinsic factor. Therefore, we believe that the mother's gastric bypass had caused a decrease in available intrinsic factor, resulting in subclinical vitamin B₁₂ deficiency and decreased breast milk B₁₂. Although she was asymptomatic, her breastfed infant developed symptomatic B₁₂ deficiency. This is the first reported case of a maternal gastric bypass resulting in vitamin B₁₂ deficiency in an infant. These mothers should receive vitamin supplements, including vitamin B₁₂ during and after pregnancy, and my require parenterally administered vitamin B₁₂.     

Nutritional Vitamin B12 Deficiency in a Breastfed Infant Following Maternal Gastric Bypass

Breasfed infants of women who have had gastric or intestinal bypass procedures may develop nutritional deficiencies. We describe a 10-month-old exclusively breastfed white male infant who presented with vomiting, failure to thrive, and megaloblastic anemia. He was found to have vitamin B₁₂ deficiency. His mother had undergone a gastric bypass procedure for morbid obesity 2 years Prior to her pregnancy with this child. She had subclinical vitamin B₁₂ deficiency, with an abnormal Schilling test that corrected with the addition of intrinsic factor. Therefore, we believe that the mother's gastric bypass had caused a decrease in available intrinsic factor, resulting in subclinical vitamin B₁₂ deficiency and decreased breast milk B₁₂. Although she was asymptomatic, her breastfed infant developed symptomatic B₁₂ deficiency. This is the first reported case of a maternal gastric bypass resulting in vitamin B₁₂ deficiency in an infant. These mothers should receive vitamin supplements, including vitamin B₁₂ during and after pregnancy, and my require parenterally administered vitamin B₁₂.     

Intact recovery from early 'acquired methylmalonic aciduria' secondary to maternal atrophic gastritis

Aim: A 6‐month‐old infant with severe hyporegenerative anaemia, muscular hypotonia and developmental delay is reported, and the metabolic, diagnostic and therapeutic implications of this case are discussed. Results: Diagnostic work‐up disclosed vitamin B12 depletion with an elevated excretion of methylmalonic acid (MMA), but a normal plasma total homocysteine. MRI showed fronto‐temporal atrophy and a delay in myelinization. The boy’s disease was attributable to a maternal atrophic gastritis. After initiation of vitamin B12 supplementation, he quickly recovered regarding haematopoiesis and MMA excretion. His neurological development completely normalized during 18 months of follow‐up including assessment by Bayley scores. Conclusion: As the majority of reported patients with this acquired form of methylmalonic aciduria show a persistent neurological deficit, early diagnosis of this condition is mandatory and should include sensitive markers of vitamin B12 depletion, namely MMA formation and plasma homocysteine.     

Nutritional vitamin B12 deficiency: Two cases detected by routine newborn urinary screening

We describe two asymptomatic newborns with nutritional vitamin B₁₂ deficiency in whom increased urinary methylmalonic acid was detected by routine neonatal screening at 3 weeks of age. Both infants were exclusively breast-fed. One mother suffered from pernicious anaemia, and the other was a strict vegetarian. Both mothers had no clinical or haematological abnormality, aside from a borderline mean corpuscular volume for the vegetarian mother. This report illustrates the early appearance of functional vitamin B₁₂ deficiency in breastfed infants of vitamin B₁₂-depleted mothers. It also demonstrates that urinary methylmalonic acid measurement is a sensitive indicator of tissue vitamin B₁₂ deficiency.     

Infant anaemia is associated with infection,low birthweight and iron deficiency in rural Bangladesh

Aim: To estimate the prevalence of infant anaemia and its association with iron deficiency, growth, infection and other micronutrient deficiencies. Methods: Using data from MINIMat, a randomized maternal food and micronutrient supplementation trial, we assessed the associations between anaemia (haemoglobin < 105 g/L) in 580 infants at 6 months and deficiencies of iron, vitamin A, vitamin B12, zinc and folate, infection and anthropometric indices. Variables associated with anaemia in bivariate analyses were evaluated in logistic regression models, adjusting for potential confounders. Results: Anaemia was found in 46% of the infants, and among these, 28% had iron deficiency (plasma ferritin <9 μg/L). Elevated C‐reactive protein (>10mg/L) (OR = 2.7, 95% CI: 1.6, 4.7), low birthweight (OR = 2.3, 95% CI: 1.5, 3.5) and iron deficiency (OR = 2.2, 95% CI: 1.4, 3.6) were independently associated with increased risk for anaemia. We also observed a seasonal variation in anaemia not mediated through the other factors studied. Conclusion: In a cohort in rural Bangladesh, anaemia at age 6 months was common and associated with infection, low birthweight and iron deficiency.     

Clinical manifestations of infants with nutritional vitamin B deficiency due to maternal dietary deficiency

Aim: In developing countries, nutritional vitamin B₁₂ deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B₁₂ deficiency are presented.
Methods: Hospital records of 27 infants diagnosed in a paediatric haematology unit between 2000 and 2008 were evaluated retrospectively.
Results: The median age at diagnosis was 10.5 months (3–24 months). All the infants were exclusively breast fed and they presented with severe nonspecific manifestations, such as weakness, failure to thrive, refusal to wean, vomiting, developmental delay, irritability and tremor in addition to megaloblastic anaemia. The diagnosis was confirmed by complete blood counts, blood and marrow smears and serum vitamin B₁₂ and folic acid levels. The median haemoglobin level was 6.4 g/dL (3.1–10.6) and mean corpuscular volume (MCV) was 96.8 fL (73–112.3). Some patients also had thrombocytopaenia and neutropaenia. All the infants showed clinical and haematological improvement with vitamin B₁₂ administration. Patients with severe anaemia causing heart failure received packed red blood cell transfusions as the initial therapy.
Conclusion: Paediatricians must consider nutritional vitamin B₁₂ deficiency due to maternal dietary deficiency in the differential diagnosis of some gastrointestinal, haematological, developmental and neurological disorders of infants with poor socioeconomic status. Delay in diagnosis may cause irreversible neurological damage.     

Vitamin B12 deficiency in a one-year-old, exclusively breast fed child

Vitamin B12 deficiency is a rare condition in children. The most frequent cause is vegetarian diet. In infants it can happen in breast fed children whose mother is on this diet. The clinical feature of the disease presents with megaloblastic anemia and symptoms such as: weakness, refusing to eat, hypotonia, paraesthesia, delayed or regressed development. We present a case report of vitamin B12 deficiency in a one-year-old, exclusively breast fed child. The mother's diet during pregnancy and breast-feeding were normal. CONCLUSIONS: The quality of the mother's diet and her haematological status during pregnancy and breast-feeding should be carefully monitored. It is necessary to introduce a variety of foods to expand the infant's diet at the proper time. The diagnosis of anaemia in the mother and/or in the child requires a careful investigation.     

Brain atrophy caused by vitamin B12-deficient anemia in an infant

Vitamin B12 deficiency in infants often presents with nonspecific hematological, gastrointestinal, and neurological manifestations. It is usually caused by inadequate intake, abnormal absorption, or congenital disorders of vitamin B12 metabolism, including transport disorders. We describe a vitamin B12-deficient infant with severe anemia who was breastfed. His mother had undiagnosed vitamin B12 deficiency having undergone total gastrectomy 18 years earlier. The infant developed normally after taking vitamin B12. It is important to suspect vitamin B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and treatment of vitamin B12 deficiency in infants is important and will help improve long-term prognosis.     

Zinc deficiency associated with anaemia among young children in rural Guatemala

One in four children younger than age five in Guatemala experiences anaemia (haemoglobin <11.0 g/dl). This study characterized the factors and micronutrient deficiencies associated with anaemia in a baseline cross‐sectional sample of 182 Guatemalan infants/toddlers and 207 preschoolers, using generalized linear mixed models. Associations between anaemia and maternal, child and household variables, and biomarkers (soluble transferrin receptor, ferritin, zinc, folate, vitamin B12, C‐reactive protein, and α1‐acid glycoprotein) were explored. Rates of anaemia were 56% among infants/toddlers and 12.1% among preschoolers. In children with anaemia, rates of iron deficiency (low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L) and zinc deficiency (serum zinc <65 μg/dl) were 81.1% and 53.7%, respectively. Folate deficiency (either plasma folate <3 ng/ml or erythrocyte folate <100 ng/ml) was 3.3%. Vitamin B12 deficiency (plasma vitamin B12 <148 pmol/L) was 7.5%. For infants and toddlers (<24 months), the odds ratio of anaemia was lower when higher number of adults lived in the household (OR = 0.69; 95% CI [0.53, 0.90]), and higher when children were zinc deficient (OR = 3.40; 95% CI [1.54, 7.47]). For preschoolers (36–60 months), the odds ratio of anaemia was lower for every additional month of age (OR = 0.90; 95% CI [0.81, 1.00]). Findings suggest that micronutrient deficiencies coexist in Guatemalan rural children, and zinc deficiency is associated with anaemia in children <24 months, highlighting the need of continued multidisciplinary interventions with multiple micronutrients. Further research examining how household composition, feeding practices, and accessibility to micronutrient supplements and to animal source foods is needed to incorporate strategies to improve the nutritional status of Guatemalan children.     

Awareness of glucose‐6 phosphate‐dehydrogenase deficiency in celiac disease

Individuals with celiac disease (CD) are predisposed to a number of haematological abnormalities including anaemia secondary to malabsorption of iron, vitamin B12 or folate; anaemia of chronic disease and coagulopathy secondary to vitamin K deficiency. Correction of coagulopathy with vitamin K is necessary before endoscopic biopsy in patients with suspected CD. However, vitamin K causes haemolysis in glucose‐6 phosphate‐dehydrogenase deficiency. Conclusion: When vitamin K administration becomes necessary for correction of coagulopathy in patients with CD; glucose‐6 phosphate‐dehydrogenase deficiency should be considered.     

Megaloblastäre Anämien durch Vitamin-B12-Mangel im Kindesalter

Background. Vitamin B12 deficiency in childhood is rare and leads to megaloblastic anemia or pancytopenia. Additionally, gastrointestinal and neurological disturbances can be found. Case report. The presented two case reports will illustrate different causes of vitamin B12 deficiency. The first report is on a 9 months old infant presenting with a dietary vitamin B12 deficiency. The second report deals with a 7 years and 6 months old girl showing a defective intestinal absorption of vitamin B12 (Imerslund-Gräsbeck syndrome). Discussion. Symptomes leading to the suspicion of a vitamin B12 deficiency are paleness, fatigue, signs of bleeding, recurrent infections, nausea, vomitting and mucosal lesions. Extreme deficiency can lead to dystrophia and regression or even arrest of neurological development. Evidence of low serum vitamin B12 levels and increased concentrations of the vitamin B12 metabolites, homocysteine in plasma and methylmalonic acid in urine, usually confirm the diagosis. Therapy. Initially intensive parenteral substitution is recommended to also influence the vitamin B12 body reserve. In cases with dietary vitamin B12 deficiency this therapy can be discontinued later on if the dietary regime has been changed. In congenital vitamin B12 malabsorption (Imerslund-Gräsbeck syndrome), parenteral vitamin B12 substitution has to be continued for the whole lifespan. Homocystein and methylmalonic acid are the most sensitive parameters to control effective therapy.