Abstract
Neuroregression in infants has varied aetiology and vitamin B12 deficiency is one of the uncommon causes. Infantile vitamin B12 deficiency is encountered in malnourished infants or in offspring of strict vegan mothers. We present two cases, both infants of 10 and 8 months of age, whose mothers had vitamin B12 deficiency. On admission, the patients were apathic, hypotonic and lethargic. Serum vitamin B12 levels were below normal limits. On cranial MRI, T2-weighted images revealed frontoparietal cortical atrophy. Both the infants responded to vitamin B12 treatment.
BACKGROUND
Neuro-regression in vitamin B12 deficiency is rare. Early recognition and intervention may be rewarding. Awareness of deficiency in strict vegetarian mothers and supplementation during pregnancy and lactation may prevent a neurological disability in the child
CASE PRESENTATION
Case 1
A 10-month-old exclusively breastfed male child born of non-consanguineous marriage was admitted to hospital with hyperpigmentation of the hands and feet for the last 4 months and failure to gain weight. He had shown regression of motor milestones in the form of loss of ability to sit, turn and hold head. He had achieved normal milestones until 6 months of age. His mother was a strict vegetarian.
On admission, the examination revealed that his weight and head circumference were below the 3rd percentile and his length was 50th percentile, he was pale, had hyperpigmentation limited to dorsum of feet and hands along with knuckle pigmentation (fig 1).
Figure 1.
Case 1: pigmentation of the hand.
The child had shown no interest in the surroundings, he did not interact and was lethargic.
He had significant generalised hypotonia, was able to sit, had head lag and had microcephaly. He had no abnormal movements. His voice was bleating in character. He moved all four limbs well.
The child was able to sit, could not pull to stand, did not reach out for objects and babbled.
Deep tendon reflexes were preserved. Examination of other systems was essentially normal.
Details of anthropometric data are given in table 1
Table 1.
Clinical profile of two cases of neuro-regression in vitamin B12 deficiency
| First case | Expected | Second case | Expected | |
| Age | 10 months | – | 8 months | – |
| Gender | Male | – | Female | – |
| Weight | 7.3 kg | 9.84 kg | 6.4 kg | 9 kg |
| OFC | 42 cm | 46 cm | 39 cm | 45 cm |
| Length | 72 cm | 73.7 cm | 63.5 cm | 70.9 cm |
| PEM grade | Grade 1 | Grade 1 |
OFC, occipitofrontal circumference; PEM, protein energy malnutrition.
His MRI brain showed frontoparietal atrophy (fig 2).
Figure 2.
Case 1: MRI of brain showing frontoparietal atrophy.
Case 2
We had a similar presentation in an 8-month-old female child, born of non-consanguineous marriage, with complaints of developmental delay, hypotonia and hyperpigmentation for 2 months’ duration.
There was regression of the motor milestones and she showed lack of interest in her surroundings. The child had developed normally and achieved milestones appropriate for her age until 6 months of age. The child was exclusively breast fed and her mother was a strict vegetarian. On examination the child was pale, had hyperpigmentation of knuckles and dorsum of hands. Her weight and head circumference were below the 3rd percentile. She was uninterested in her surroundings and did not interact.
She had generalised hypotonia, there was head lag, she moved all of her four limbs well and had no abnormal movements. She was able to sit up but her head wobbled. She had a bleating voice. Her deep tendon reflexes were preserved. The rest of her physical examination was normal.
Detailed clinical and laboratory profiles of both case 1 and 2 are given in tables 1 and 2.
Table 2.
Laboratory profiles of the two cases
| First case | Second case | Normal values | |
| Haemoglobin | 5 g/dL | 8.9 g/dL | 10–14 g/dl |
| MCV | 85 fl | 96.7fl | 70–85 fl |
| MCH | 30 pg | 31 pg | 23–31 pg |
| RDW | 39.1% | 23.1% | 14.4% |
| B12 levels | 71 pg/mL | 119 pg/mL | 311–711 pg/mL |
| Folic acid | 7 ng/mL | 12 ng/mL | 5–20 ng/mL |
| Iron | 98 mic/dL | 84 mic/dL | 22–184 mic/dL |
| PS | Macrocytosis with hypochromic with normal leucocytes and platelets | Macrocytosis | |
| Hypochromia | |||
| Normal leucocytes and platelets | |||
| MRI brain | Cerebralatrophy frontoparieto temporal region with delayed myelination for age | Cerebral atrophy frontoparital region with delayed myelination for age |
MCH, mean corpuscular haemoglobin; MCV, mean corpuscular volume; PS, peripheral smear; RDW, red cell distribution width.
INVESTIGATION
Details are given in table 2.
TREATMENT
Both were given intramuscular injections of 1000 μg of vitamin B12 daily for 2 weeks (injection cynocobalamin available in multidose vial, each ml containing 1000 mcg).
OUTCOME AND FOLLOW-UP
After 14 days they were reassessed. Both the infants were regaining milestones and showed much improved social behaviour. The hyperpigmentation of the dorsum of the feet and hands diminished. Hair colour improved from hypopigmented to normal. Their improvement was further assessed by repeat MRI after 28 days, which showed improved in the cerebral atrophy.
DISCUSSION
In exclusively breastfed infants, the cobalamin content in the milk and, therefore, the maternal cobalamin status during lactation, has a profound impact on the infant cobalamin status.1 Infant cobalamin deficiency is considered secondary to maternal deficiency, which may be attributable to vegetarianism, malabsorption or unrecognised early pernicious anaemia. High rates of cobalamin deficiency in pregnant and breastfeeding women and their infants have repeatedly been demonstrated in developing countries.2,3 In developed countries, exclusive breast feeding for the first 6 months is encouraged and this places great nutritional demands on the mother.
Vegetarian diets may be classified as lacto-vegetarian, ovo-vegetarian, lacto-ovo-vegetarian or vegan if they include dairy products, eggs, both dairy products and eggs or no animal products at all, respectively.
In our cases, the cause of the vitamin deficiency was because of a strict vegetarian diet.
Vitamin B12 deficiency in children differs from that in adults in aetiology, clinical presentation and radiological findings.4–6 Severe neurological findings ranging from hypotonia, apathy decreased visual contact, adynamia and lethargy, or even coma may accompany anaemia.
Another distinct finding was the hyperpigmentation of the dorsal sites of the hands in our patients. This distinct finding may be significant in vitamin B12 deficiency. Generalised hyperpigmentation is a well-defined finding in patients with vitamin B12 deficiency.5
MRI findings in infantile vitamin B12 deficiency differ from those in adults in that subacute combined degeneration of spinal cord is detected in adults,7 whereas in infants cerebral atrophy is seen.8,9
Although many of the metabolic disturbances resulting from vitamin B12 deficiency are understood, the pathogenesis of the nervous system abnormalities is unknown.
Several cofactors derived from vitamin B12 are necessary for the conversion of homocysteine to methionine and methylmalonyl-CoA to succininyl-CoA and, when these cofactors are unavailable, abnormal levels of homocysteine are found in the blood and excessive methylmalonic acid is excreted in the urine. Treatment with vitamin B12 corrects these metabolic abnormalities very rapidly within a few days.
Both our patients presented to us 2 and 4 months after onset of their illnesses due to various reasons. The importance of early recognition of significant maternal vitamin B12 deficiency during pregnancy and lactation in vegetarians is emphasised so that appropriate supplementation can be given and irreversible neurological damage in the infant prevented.
Although early response to treatment is satisfying, the long-term consequences of nutritional vitamin B12 deficiency in infants emphasise the need for prevention or early recognition of this syndrome.10
Vitamin B12 deficiency may cause lasting neurological disability despite improvement in cerebral atrophy and in electroencephalography abnormalities.11
LEARNING POINTS
Vitamin B12 deficiency may be a cause of generalised hypotonia and neuro-regression and simple clues may come from a haemogram.
In strict vegans, B12 deficiency may occur and this during pregnancy and lactation may cause deficiency in the exclusively breastfed child.
Early recognition and treatment may help neurological recovery.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
REFERENCES
- 1.Bjørke-Monsen A-L, Torsvik I, Sætran . Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation. Pediatrics 2008; 122: 83–91 [DOI] [PubMed] [Google Scholar]
- 2.Allen LH. Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol 1994; 352:173–86 [DOI] [PubMed] [Google Scholar]
- 3.Weiss R, Fogelman Y, Bennett M. Severe vitamin B12 deficiency in an infant associated with a maternal deficiency and a strict vegetarian diet. J Pediatr Hematol Oncol 2004; 26: 270–1 [DOI] [PubMed] [Google Scholar]
- 4.Casella EB, Valente M, de Navarro JM, et al. Vitamin B12 deficiency in infancy as a cause of developmental regression. Brain Dev 2005; 27: 592–4 [DOI] [PubMed] [Google Scholar]
- 5.Emery ES, Homans AC, Colletti RB. Vitamin B12 deficiency: a cause of abnormal movements in infants. Pediatrics 1997; 99: 255. [DOI] [PubMed] [Google Scholar]
- 6.Sharma S, Khilnani GC, Berry M. Case of season. Megaloblastic anemia with subacute combined degeneration (SCD) of the spinal cord. Semin Roentgenol 1999; 34: 2–4 [DOI] [PubMed] [Google Scholar]
- 7.Bassi SS, Bulundwe KK, Greeff GP, et al. MRI of the spinal cord in myelopathy complicating vitamin B12 deficiency: two additional cases and review of the literature. Neuroradiology 1999; 41: 271–4 [DOI] [PubMed] [Google Scholar]
- 8.Lövblad K, Ramelli G, Remonda L. Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings. Pediatr Radiol 1997; 27: 155–8 [DOI] [PubMed] [Google Scholar]
- 9.Avci Zekai, Turul Tuba, Aysun Sabiha, et al. Involuntary movements and magnetic resonance imaging findings in infantile cobalamine (vitamin B12) deficiency. Pediatrics 2003; 112: 684–6 [DOI] [PubMed] [Google Scholar]
- 10.Graham SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 1992; 121: 710–14 [DOI] [PubMed] [Google Scholar]
- 11.Schenck UV, Bender-Götze C, Koletzko B. Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy. Arch Dis Child 1997; 77: 137–9 [DOI] [PMC free article] [PubMed] [Google Scholar]