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In infants with nutritional vitamin B12 deficiency, early clinical symptoms follow a consistent pattern with irritability, failure to thrive, apathy and anorexia, accompanied by consistent refusal of solid foods and developmental regression. Vitamin B12 acts as a cofactor in the remethylation of homocysteine and the degradation of methylmalonyl-CoA. The biochemical mechanisms by which vitamin B12 deficiency leads to neurological damage are poorly understood. We report on seven breast fed infants with nutritional vitamin B12 deficiency due to maternal vegan diet. Tables 1–3 give clinical, radiological, and laboratory findings. Increased excretion of methylmalonic acid in the urine as well as increased total homocysteine in the plasma were found in all the patients. There was no clear correlation with the severity of acute neurological symptoms. Accumulation of methylmalonyl-CoA is known to interfere with the biosynthesis of lipids needed for myelin sheaths. Delayed myelination was observed in patient 4, and reversible brain atrophy was seen in all patients examined.
Disruption of the methionine cycle and lack of S-adenosylmethionine, the most important methyl group donor, may lead to accumulation of neurotoxic guanidinoacetate.1 We found normal plasma concentrations of guanidinoacetate in three patients examined. It has been speculated in a single case report whether the thermolabile MTHFR polymorphism C677T aggravates neurological damage or leads to delayed recovery by further impairing the folate cycle.2 Molecular analysis of the MTHFR gene was normal in six of our patients making it impossible to assess the relation to clinical severity or recovery.
The early presentation and adverse outcome in patient 3 would support the hypothesis that the prognosis of infantile vitamin B12 deficiency is related to the age of onset.3 As patient 3 showed no other clinical signs of vitamin B12 deficiency at the time of diagnosis, a coincidence of idiopathic BNS epilepsy leading to the diagnosis of vitamin B12 deficiency by chance cannot be ruled out.
In our opinion the severity and prognosis of infantile vitamin B12 deficiency cannot be related to a single biochemical variable. Additional measurement of methionine and S-adenosylmethionine in plasma and methyl tetrahydrofolate in cerebrospinal fluid should be performed. Paediatricians should be aware of nutritional vitamin B12 deficiency in breast fed infants, as immediate and appropriate treatment is mandatory.
Competing interests: none declared
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