Key words: cobalamin, infant, deficiency, and abnormal movement.

Cobalamin deficiency typically occurs in middle aged and elderly patients. It isconsidered to be rare in infants when it is usually secondary to maternal deficiency.

Most of the infants found to be cobalamin deficient were breast fed or born to vegetarian mothers. Under these conditions there is probably insufficient cobalamin transfer across the placenta which leads to low cobalamin stores in the newborn. This deficiency is further deteriorated by insufficient cobalamin in breast milk of vegetarian mothers [1]. These infants can exhibit a prominent disorder of movement [3], severe neurological findings ranging from apathy, decreased visual contact, adynamia, and lethargy or even coma may accompany anemia [9].

An 11 months old black female infant, exclusively breast fed, low socioeconomic status, failure to thrive, developmentally delayed, admitted to Prince Ali hospital with abnormal twitching movement of the right side of the face and right upper limb.

On examination she was pale her weight below 5th percentile, head circumference on 5th percentile, and normal height. She had global developmental delay, there was twitching movement involving the right side of the face and right upper limb, no other abnormal neurological signs, normal power, tone and reflexes. Other systems
examination was normal.

Investigations showed low PCV 25%, high MCV 105 fl, neutropenia with hypersegmentation, and normal retics count. KFT normal, low albumin, other LFT normal, B12 level low =65pg/ml, normal folate and ferritin level, ABG normal, sweat chloride test normal. Antiglidin Abs, antiendomesial Abs are negative. Brain MRI normal and maternal B12 is low 150pg/ml.

The patient was started on B12 IM 1mg daily for two weeks, Halidol drops were given for 3 weeks, but no response to treatment. Patient then was maintained on monthly 1mg B12 IM injection and was followed up in clinic. After three months of treatment, the patient showed complete resolution of the twitching movements, and laboratory disorders.

Vitamin B12 is derived from cobalamin in food, mainly animal sources, secondary to production by microorganisms. The cobalamins are released in the acidity of the stomach and combine there with R proteins and intrinsic factor, traverse the duodenum, where pancreatic proteases break down the R proteins, and are absorbed in distal ileum [4].

Although there are abundant vitamin B-12-producing bacteria that colonize the large bowel, that organ is too distal to allow normal vitamin B-12 absorption [2].

The daily requirements for vitamin B12 in infants is 0.3-0.5 mcg, for children 0.7-1.4 mcg, for adult 2.0mcg,and for pregnant and lactating mother 2.6mcg [4].

There are two active forms of cobalamin in human body, deoxyadenosylcobalamin and methylcobalamin. Deoxyadenosylcobalamin is a required cofactor for conversion of methylmalonyl- CoA to succinyl- CoA and in its deficiency lead to incorporation of nonphysiologic fatty acids into cell membranes of CNS which may be responsible for neurological manifestations of cobalamin deficiency. While methylcobalamin is required for the formation of H4folate, and conversion of homocysteine to methionine, H4folate is required for DNA synthesis [5,7]. While methionine is further metabolized to s-adenosylmethionine (SAM) which play arole in myelin and neurotransmitters synthesis and maintenance [6].

Another metabolite implicated in CNS manifestations is N-methyl-D-aspartate agonist action of homocysteine, which causes excitatory activity in basal ganglia by means of thalamocortical pathway [8]. Hyperglycinemia secondry to cobalamin deficiency is also implicated as a cause of abnormal movement [3,9].

Decrease in cognitive function in patients with vitamin B12 deficiency is related to hyperhomocysteinemia [1].

Symptoms and signs of cobalamin deficiency appears between ages of 2-12 months including vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of development [3]. Although these symptoms may appear even without anemia [1,7].

A syndrome of nutritional dystrophy and anemia, first described in 1957, was found exclusively among breastfed infants of Indian mothers of extremely low socioeconomic status. Although these infants had adequate general nutrition, they also had apathy, megaloblastic anemia, skin hyperpigmentation, involuntary movements, and developmental regression that were rapidly corrected by vitamin B-12 [2].

Approximately 50% of the infants with vitamin B12 deficiency exhibit abnormal movements manifested as tremor, twitches, chorea, or myoclonus. These movements can appear several days following the start of treatment [3]. Grattan-Smith et al reported the movement disorder that appeared after treatment, as that after a period of severe shortage, the sudden availability of cobalamin resulted in intense stimulation of cobalamin and folate pathways and produced a temporary inbalance of metabolic pathways (9).

The duration of these abnormal movements has ranged from 10-30 days [3], but in ourpatient twitches resolved after 3 months of treatment.

Generalized hyperpigmentation is a well-defined finding in patients with vit B12 deficiency [9], but it was not detected in our case (black infant).
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In evaluating vitamin B12 status, CBC which show MCV>94fl is considered suspicious for vitamin B12 deficiency, but neutrophil hypersegmentation is the only hematological change that correlates well with vitamin B12 deficiency [7]. In our patient MCV was 105fl and neutrophilic hypersegementation was detected.

Measurement of serum vitamin B12 is considered the cornerstone for assessing suspected cases of vitamin B12 deficiency, but it is altered by the concentration of the binding proteins, which causes false high or low values [7]. Serum B12 in our patient was low 65pg/ml. High levels of MMA and homocystein are more sensitive and specific for vitamin B12 deficiency [7], but unfortunately these tests are not available in our lab.

MRI findings in infantile vit B12 deficiency differ from those of adult forms. In adults subacute combined degeneration of spinal cord is detected, whereas in infants cerebral atrophy is seen [9]. In our patient brain MRI was normal.

Treatment of infants with vitamin B12 deficiency with CNS manifestations is byparental injection of vitamin B12 1mg daily for two weeks. Permanent treatment with monthly IM injection of 1mg vitamin B12 is required [4].

Treatment with vitamin B12 can reverse all the adverse effects but permanent sequelae may result [3].

The long-term consequences include poor intellectual performance and impaired cognitive function [1].

Although cobalamin deficiency is rare in infancy, it should be considered as a cause of failure to thrive, developmental delay, and movement disorder.

Prevention, early recognition, and treatment are required to avoid permanent long-term sequelae.