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PEDIATRICS Vol. 112 No. 3 September 2003, pp. 684-686

EXPERIENCE AND REASON

Involuntary Movements and Magnetic Resonance Imaging Findings in Infantile Cobalamine (Vitamin B₁₂) Deficiency

Zekai Avci, MD

Department of Pediatrics
Fatih University School of Medicine
Ankara, Turkey

Tuba Turul, MD and Sabiha Aysun, MD

Department of Pediatrics
Hacettepe University School of Medicine
Ankara, Turkey

Iil Ünal, MD

Department of Neurology
Hacettepe University School of Medicine
Ankara, Turkey

Abbreviations: EMG, electromyography • Ig, immunoglobulin • MRI, magnetic resonance imaging • vit B₁₂, vitamin B₁₂

Infantile vitamin B₁₂ (vit B₁₂) deficiency is encountered in malnourished infants or in offspring of strict vegan mothers or mothers with pernicious anemia and accompanied by hematologic and neurologic findings. We present here a 16-month-old infant whose mother had vit B₁₂ deficiency with low socioeconomic level admitted to our hospital. On admission, the patient was apathic, hypotonic, and lethargic. Serum vit B₁₂ level was below detectable limits. On cranial magnetic resonance imaging (MRI), T2-weighted images revealed bilateral frontal and parietal periventricular high-signal symmetric lesions in the white matter (delayed myelination) and frontoparietal cortical atrophy. On day 3 of vit B₁₂ therapy, involuntary movements were observed.

Vit B₁₂ is an essential vitamin and needs to be supplied by diet. Although a vit B₁₂-deficient diet can be tolerated by the adults for years from the endogenous pool, deficiency in infants may become symptomatic in a few months because of the limited hepatic reserve.¹ Infantile vit B₁₂ deficiency is common in malnourished offspring of vegan mothers and mothers with pernicious anemia and has a clinical course of ineffective hematopoiesis and neurodegenerative signs.^1–5 Here, we present a 16-month-old male infant who had severe vit B₁₂ deficiency accompanied by hematologic, neurologic, and typical MRI findings.

	CASE REPORT

TOP CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
A 16-month-old male infant was admitted to our hospital for fever and tendency to sleep. His past medical history revealed that his mental and motor development were normal up to 8 months of age. He subsequently became lethargic and showed developmental regression. He was hospitalized for irritability and apathy during the course of a pulmonary infection.

He was the second child to nonconsanguineous parents with low socioeconomic status. He was delivered at term following an uneventful delivery. His birth weight was 3250 g. He was breastfed until 16 months of age.

On admission, he was hypoactive, lethargic, and not following objects visually with mild dysmorphic features. He was malnourished; length: 74 cm (<3rd percentile), weight: 9 kg (<3rd percentile), and head circumference: 45 cm (<3rd percentile). He had hyperpigmentation on the dorsum of the hands, fine hair, glossitis, and hepatomegaly. He was able to sit with support and had no head control. He was generally hypotonic but had normal strength and brisk reflexes. Cranial nerve examination was normal.

A complete blood count showed macrocytic anemia (hemoglobin 5.1 g/dL, mean corpuscular volume 103.8 fl). Macrocytosis and anisocytosis were noted. The serum vit B₁₂ level was below detectable limits (limit of detection is 45 pg/mL, normal range: 157-1059 pg/mL) and serum folic acid level was 11.5 ng/dL (normal range: 5.3–14.4 ng/dL). His bone marrow aspiration revealed significant megaloblastic features. A thorough work up including blood gases, direct Coomb’s test, electrolyte levels, hemoglobin F, lactic acid, pyruvic acid, ammonium level, biotinidase activity, thyroid function tests, electrocardiography, and echocardiography were found to be normal. Serum immunoglobulin (Ig) G and IgM level were 400 mg/dL (normal range: 605-1430 mg/dL) and 31 mg/dL (normal range: 66–228 mg/dL), respectively; IgA level and other immunologic tests including lymphocyte subsets, spesific antibody responses, and in vitro lymphocyte proliferation were normal. Electroencephalography on admission was normal. Electromyography (EMG) was compatible with a peripheral neuropathy. MRI of the head revealed bilateral frontoparietal cortical atrophy (Fig 1) and bilateral frontal and parietal periventricular high-signal symmetric lesions in the white matter on T2-weighted images (Fig 2).

View larger version (122K): [in this window] [in a new window]   Fig 1. Cranial MRI of the patient revealed severe cortical atrophy on T1-weighted section.

 

View larger version (134K): [in this window] [in a new window]   Fig 2. Bilateral periventricular symmetric high-signal lesions in the white matter on T2-weighted images.

 
His mother’s serum vit B₁₂ level was also low at 125 pg/mL and her folic acid level was normal.

His diet was supported by essential elements (ZnSO₄ 50 µg/day, MgOH₂ 200 µg/day) and he was put on intramuscular vit B₁₂ (100 µg/every other day). On day 3 of therapy, he developed smacking and twitching movements of the lips and marked tremor of the tongue. On the third week he showed tremor of the left arm to tactile stimulation and on arousal. Biperidene hydrochlorate (0.5 mg 3 times daily) was added to control involuntary movements. Involuntary movements decreased after the first week of the biperidene hydrochlorate therapy. Three months later, on examination, it was observed that hypotonia, hipoactivity and involuntary movements, and hiperpigmentation on the dorsum of the hands had already disappeared. MRI findings were observed to be decreased. Today our patient is 3.5 years old and he has near normal mental and motor development.

	DISCUSSION

TOP CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
Vit B₁₂ deficiency may have complex clinical presentation associated with hematologic, neurologic, and psychiatric symptoms. Infantile vit B₁₂ deficiency was first defined in 6 South Indian infants, ages between 7 and 12 months in 1962.⁶

Vit B₁₂ deficiency in children differs from the adults by etiologic factors, clinical presentation, and radiologic findings. It is common in the infants of the mothers with pernicious anemia, mothers who are malnourished because of low socioeconomic condition or who are on a strict vegan diet. Severe neurologic findings ranging from hypotonia, apathia, decreased visual contact, adynamia and lethargy, or even coma may accompany anemia.^1,3,4,9 In contrast to severe neurologic findings in infantile cobalamine deficiency, in adolescents and adults only mild neuropsychiatric symptoms are observed.^7,8 In a study of adolescents who have no hematologic abnormalities, the cognitive performance of the cobalamine-deficient group who take a vegan diet with marginal vit B₁₂ status was found to be lower than the control group.⁷

Although hypotonia is a frequent sign of vit B₁₂ deficiency in infancy,^1,3,5 correlation with EMG findings was rarely reported. Similar to our case, Renault et al⁴ reported 2 infants with severe hypotonia and apathy who had peripheral sensory motor neuropathy confirmed by EMG. The mechanism responsible for neuropathy is not clearly understood yet; however, several explanations have been suggested.^10–13

The reason why he developed involuntary movements during cobalamin therapy is not clear. Similar conditions have been previously reported in the vit B₁₂-deficient infants.^4,5,9 Hyperglycinemia causing nonspecific interference with glycine cleavage was suggested to be responsible for abnormal movements. However, normal glycine levels in symptomatic patients excluded this hypothesis.^14,15 On the other hand, Grattan-Smith et al⁵ reported the movement disorder that appeared after treatment is 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, with local deficiencies or excesses occurring. A metabolite that has not been demonstrated yet may be responsible for the involuntary movements.

Another distinct finding was the hyperpigmentation of the dorsal sites of the hands in our patient. This distinct finding may be significant in vit B₁₂ deficiency. Generalized hyperpigmentation is a well-defined finding in patients with vit B₁₂ deficiency.⁶ To our knowledge, this is the first case reported to have localized hyperpigmentation.

Vit B₁₂ deficiency may lead to low serum IgG and IgM levels as seen in our patient. In a study on rats with vit B₁₂ deficiency, serum IgG and IgM levels were found to be decreased.¹⁶ In our case, serum IgG and IgM levels normalized after vit B₁₂ treatment, so within it was related with vit B₁₂ deficiency.

MRI findings in infantile vit B₁₂ deficiency differ from those of adult form. In adults subacute combined degeneration of spinal cord is detected,^3,17,18 whereas in infants cerebral atrophy and is seen.^1,5 In our patient, cranial MRI showed symetric high-signal lesions in the white matter of both frontal and parietal lobes on T2-weighted images in addition to diffuse cerebral atrophy.

	CONCLUSION

TOP CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
Vit B₁₂ deficiency may be seen in infants and present with distinct clinical and MRI findings.

	FOOTNOTES

 
Received for publication Oct 2, 2001; Accepted Jan 6, 2003.

Reprint requests to (Z.A.) Department of Pediatrics, Fatih University School of Medicine, Alparslan Türkeþ cad. No: 57, 06510, Beþtepe, Ankara, Turkey. E-mail: zekaiavci{at}yahoo.com

	REFERENCES

TOP CASE REPORT DISCUSSION CONCLUSION REFERENCES

 

1. 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 –139[Abstract/Free Full Text]
2. Kalayci Ö, Çetin M, Kirel B, et al. Neurologic findings of vitamin B-12 deficiency: presentation of 7 cases. Turk J Pediatr.1996; 38 :67 –72[Web of Science][Medline]
3. Graham SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin B₁₂ deficiency in infants. J Pediatr.1992; 121 :710 –714[CrossRef][Web of Science][Medline]
4. Renault F, Verstchel P, Ploussard JP, Costil J. Neuropathy in two cobalamin-deficient breast-fed infants of vegetarian mothers. Muscle Nerve.1999; 22 :252 –254[CrossRef][Web of Science][Medline]
5. Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord.1997; 12 :39 –46[CrossRef][Web of Science][Medline]
6. Jadhav M, Webb JKG, Vaishnava S, Baker SJ. Vitamin-B₁₂ deficiency in Indian infants. Lancet.1962; ii :903 –907
7. Louwman MW, van Dusseldorp M, van de Vijver FJ, et al. Signs of impaired cognitive function in adolescent with marginal cobalamin status. Am J Clin Nutr.2000; 72 :762 –769[Abstract/Free Full Text]
8. Goebels N, Soyka M. Demantia associated with vitamin B₁₂ deficiency: presentation of two cases and review of the literature. J Neuropsychiatry Clin Neurosci.2000; 12 :389 –394[Abstract/Free Full Text]
9. Emery SE, Homans AC, Colletti RB. Vitamin B₁₂ deficiency: a cause of abnormal movements in infants. Pediatrics.1997; 99 :255 –256[Free Full Text]
10. Frenkel H. Abnormal fatty acid metabolism in peripheral nerve of patients with pernicious anemia. J Clin Invest.1973; 52 :1237 –1245
11. Cooper BA, Rosenblatt DS. Inherited defects of vitamin B12 metabolism. Annu Rev Nutr.1987; 7 :291 –320[Web of Science][Medline]
12. Carmel R, Wathuis D, Goodman SI, Rosenblatt DS. Heriditary defects of cobalamin metabolism (CbIG-mutation) presenting as a neurological disorder in childhood. N Engl J Med.1988; 318 :1738 –1741[Web of Science][Medline]
13. Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B₁₂) and folate deficiency. FASEB J.1993; 7 :1344 –1353[Abstract]
14. Higginbottom MC, Sweetman L, Nyhan WL. A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B₁₂-deficient breast-fed infant of a strict vegetarian. N Engl J Med.1978; 299 :317 –323[Abstract]
15. Kuhne T, Bubl R, Baumgartner R. Maternal vegan diet causing a serious infantile neurologic disorder due to vitamin B₁₂ deficiency. Eur J Pediatr.1991; 150 :205 –208[CrossRef][Web of Science][Medline]
16. Funada U, Wada M, Kawata T, et al. Changes in CD4+CD8–/CD4–CD8+ ratio and humoral immune functions in vitamin B₁₂-deficient rats. Int J Vitam Nutr Res.2000; 70 :167 –171[CrossRef][Web of Science][Medline]
17. 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[CrossRef][Web of Science][Medline]
18. Bassi SS, Bulundwe KK, Greeff GP, Labuscagne JH, Gledhill RF. MRI of the spinal cord in myelopathy complicating vitamin B₁₂ deficiency: two additional cases and review of the literature. Neuroradiology.1999; 41 :271 –274[CrossRef][Web of Science][Medline]

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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Avci, Z. Articles by Ünal, I. Search for Related Content PubMed PubMed Citation Articles by Avci, Z. Articles by Ünal, I. Related Collections Neurology & Psychiatry Social Bookmarking                         What's this?