Cobalamin deficiency in children: A literature review

Abstract

Objective: The aim of this review is to present cobalamin deficiency in children with a specific focus on infants. Background: Cobalamin deficiency is caused by inadequate intake, malabsorption or inborn errors of vitamin B12 metabolism. Cobalamin deficiency in infants is usually caused by deficiency in the mother. There is often a diagnostic delay among infants because the most frequent symptoms are unspecific, e.g., developmental delay, apathy, hypotonia, anorexia and failure to thrive. Children with longstanding cobalamin deficiency are at risk of permanent neurologic sequelae. Method: A literature search in Medline was performed in July 2013 using the words cobalamin deficiency with focus on reviews and clinical trials involving children. A total of 25 articles were reviewed. Medical records of children with the diagnosis cobalamin deficiency admitted at Oslo University Hospital during the period 2000-2012, were also reviewed. Results and conclusion: The diagnosis of cobalamin deficiency is not always straightforward: Relying on serum cobalamin levels alone is unspecific and supplemental measurements of total homocysteine (tHcy) and methylmalonic acid (MMA) are recommended. Megaloblastic anemia, which is considered by many to be typical in cobalamin deficiency, is often lacking and is probably a late sign. There is no international consensus on the definition of cobalamin deficiency in children or on which reference limits one should use for serum cobalamin, tHcy and MMA. New reference limits for serum cobalamin, tHcy and MMA which are adjusted for age, sex and pregnancy should be investigated. Some, but far from all infants with cobalamin deficiency, are discovered due to detection of elevated propionylcarnitine (C3) in the newborn screening program, but an expanded newborn screening project with measurements of C3, C3/C2 ratio, tHcy and MMA would increase the sensitivity and specificity considerably. Possible preventive measures include cobalamin supplementation to pregnant and nursing women, to newborns or to the population in general. The prevalence of significant cobalamin deficiency in infants is uncertain, but indications suggest that it is an underdiagnosed condition. More studies are needed to estimate prevalence more accurately.

Objective: The aim of this review is to present cobalamin deficiency in children with a specific focus on infants. Background: Cobalamin deficiency is caused by inadequate intake, malabsorption or inborn errors of vitamin B12 metabolism. Cobalamin deficiency in infants is usually caused by deficiency in the mother. There is often a diagnostic delay among infants because the most frequent symptoms are unspecific, e.g., developmental delay, apathy, hypotonia, anorexia and failure to thrive. Children with longstanding cobalamin deficiency are at risk of permanent neurologic sequelae. Method: A literature search in Medline was performed in July 2013 using the words cobalamin deficiency with focus on reviews and clinical trials involving children. A total of 25 articles were reviewed. Medical records of children with the diagnosis cobalamin deficiency admitted at Oslo University Hospital during the period 2000-2012, were also reviewed. Results and conclusion: The diagnosis of cobalamin deficiency is not always straightforward: Relying on serum cobalamin levels alone is unspecific and supplemental measurements of total homocysteine (tHcy) and methylmalonic acid (MMA) are recommended. Megaloblastic anemia, which is considered by many to be typical in cobalamin deficiency, is often lacking and is probably a late sign. There is no international consensus on the definition of cobalamin deficiency in children or on which reference limits one should use for serum cobalamin, tHcy and MMA. New reference limits for serum cobalamin, tHcy and MMA which are adjusted for age, sex and pregnancy should be investigated. Some, but far from all infants with cobalamin deficiency, are discovered due to detection of elevated propionylcarnitine (C3) in the newborn screening program, but an expanded newborn screening project with measurements of C3, C3/C2 ratio, tHcy and MMA would increase the sensitivity and specificity considerably. Possible preventive measures include cobalamin supplementation to pregnant and nursing women, to newborns or to the population in general. The prevalence of significant cobalamin deficiency in infants is uncertain, but indications suggest that it is an underdiagnosed condition. More studies are needed to estimate prevalence more accurately.