A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B<sub>12</sub>-Deficient Breast-Fed Infant of a Strict Vegetarian

Higginbottom, Marilyn C.; Sweetman, L.; Nyhan, William L.

doi:10.1056/nejm197808172990701

Cited by 252 publications

(89 citation statements)

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“…The metabolic abnormalities found in the affected dogs were similar to those found in Cbl-deficient humans and other species. Cbl deficiency in the inadequately treated proposita caused low serum Cbl concentrations and methylmalonic aciduria in her otherwise normal, heterozygous puppies until weaning, as has been reported in human infants nursed by strict vegetarians or mothers with untreated pernicious anemia (33,34). In subsequent gestations, the proposita received more aggressive Cbl therapy, and only her affected puppies became Cbl deficient.…”

Section: Discussionmentioning

confidence: 52%

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

et al. 1991

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ABSTRACT. Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-I1 from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Grasbeck syndrome)

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Section: Discussionmentioning

confidence: 52%

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

et al. 1991

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“…[18][19][20] Several studies report severe neurological effects and classical demyelination lesions in infants of mothers on diets that are deficient in vitamin B 12 . [21][22][23] Although this study did not focus on deficient versus non-deficient groups, lower levels of vitamin B 12 could contribute to the changes in autonomic regulation such as an increased heart rate. Furthermore, low vitamin B 12 and folate concentrations are linked to high homocysteine concentrations.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B₁₂ and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5–6 years: findings from the ABCD multi‐ethnic birth cohort

Krikke

Grooten

Vrijkotte³

et al. 2015

BJOG

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Objective To explore whether maternal vitamin B 12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6.Design Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD). Population Mother-child pairs for whom information on maternal vitamin B 12 or folate status in early gestation and health at age 5-6 years was available (n = 1950).Methods Vitamin B 12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders.Main outcome measures Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6.Results Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: b 0.07 kg/m 2 , 95% confidence interval (CI) 0.01, 0.13].Low maternal vitamin B 12 concentrations were associated with higher heart rates (decrease per 100 units: b 0.49 beats/min, 95% CI 0.11, 0.87).Conclusion This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring.Keywords Body mass index, folate, heart rate, offspring, pregnancy, vitamin B 12 .Tweetable abstract Low folate and vitamin B 12 levels during pregnancy are associated with higher BMI and heart rate in offspring.Please cite this paper as: Krikke GG, Grooten IJ, Vrijkotte TGM, van Eijsden M, Roseboom TJ, Painter RC. Vitamin B 12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5-6 years: findings from the ABCD multi-ethnic birth cohort. BJOG 2016;123:384-392.

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“…Several case reports, mainly from developing countries (1,5,6 ), demonstrate the importance of maintaining adequate cobalamin concentrations during periods of rapid growth and development. In infancy, cobalamin deficiency may present as failure to thrive, developmental delay and regression, progressive neurologic disorders, or hematologic changes.…”

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confidence: 99%

Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years

Monsen¹,

Refsum

Markestad³

et al. 2003

Clinical Chemistry

115

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Background: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year. Methods: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years. Results: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 mol/L), median plasma tHcy was low (<6 mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r ‫؍‬ ؊0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (<6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r ‫؍‬ ؊0.52) but not to serum folate in infants <6 months. In older children, tHcy showed the expected association with both cobalamin (r ‫؍‬ ؊0.48) and folate (r ‫؍‬ ؊0.51).

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A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B₁₂-Deficient Breast-Fed Infant of a Strict Vegetarian

Cited by 252 publications

References 25 publications

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

Vitamin B₁₂ and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5–6 years: findings from the ABCD multi‐ethnic birth cohort

Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years

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A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B12-Deficient Breast-Fed Infant of a Strict Vegetarian

Cited by 252 publications

References 25 publications

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5–6 years: findings from the ABCD multi‐ethnic birth cohort

Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years

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A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B₁₂-Deficient Breast-Fed Infant of a Strict Vegetarian

Vitamin B₁₂ and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5–6 years: findings from the ABCD multi‐ethnic birth cohort