Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2019; 18: 70-77
Витамин В12-дефицитная анемия у детей грудного возраста: клиническая картина, современные методы диагностики и лечения
https://doi.org/10.24287/1726-1708-2019-18-3-70-77Аннотация
Дефицит витамина В12 (кобаламина) у детей, находящихся исключительно на грудном вскармливании, – обычно результат его дефицита у матерей (вегетарианки, с нераспознанной пернициозной анемией или синдромом мальабсорбции). Кобаламин имеет решающее значение для нормального развития нервной системы, производства эритроцитов и синтеза ДНК. Классическое проявление его дефицита – мегалобластная анемия, в продвинутых ее стадиях – панцитопения. Однако у маленьких детей превалирует неврологическая симптоматика (регресс навыков развития, летаргия, двигательные расстройства) как следствие неадекватной миелинизации головного мозга. На фоне терапии кобаламином у большинства детей неврологическая симптоматика регрессирует, однако может сохраняться неврологический дефицит разной выраженности. Долгосрочный прогноз зависит от длительности дефицита витамина В12. В статье приведены собственные интересные клинические наблюдения. Родители пациентов дали согласие на использование информации о ребенке в научных исследованиях и публикациях.
Список литературы
1. Kliegman R.M., Stanton B.F., St. Geme J.W., 3rd, Schor N.F., Behrman R.E. Vitamin B12 (Cobalamin). In: Sachdev HPS, Shah D, editors; Nelson textbook of pediatrics. 19th ed. Philadelphia, PA: Saunders; 2011; pp. 197–8.
2. Schrier S.L. Hematology ASH, and the anemia of the aged. Blood 2005; 106 (10): 3341–2.
3. de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008; 29: S238–44.
4. Karaoglu L., Pehlivan E., Egri M., Deprem C., Gunes G., Genc M., et al. Research article The prevalence of nutritional anemia in pregnancy in an east Anatolian province, Turkey. BMC Public Health 2010; 10: 329.
5. Oh R.C., Brown D.L. Vitamin B12 Deficiency Am Fam Physician 2003 Mar 1; 67 (5): 979–86.
6. Rasmussen S.A., Fernhoff P.M., Scanlon K.S. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001; 138: 10–7.
7. Allen L.H. Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol 1994; 352: 173–86.
8. Bjørke Monsen A.L., Ueland P.M., Vollset S.E., Guttormsen A.B., Markestad T., Solheim E., et al. Determinants of cobalamin status in newborns. Pediatrics 2001; 108: 624–30.
9. Румянцев А.Г., Масчан А.А., Демихов В.Г., Скобин В.Б., Журина О.Н. Феде-ральные клинические рекомендации по диагностике и лечению анемии, обусловленной дефицитом В12. – М., 2015.
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11. Dror D.K., Allen L.H. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev 2008; 66 (5): 250–5.
12. Pepper M.R., Black M.M. B12 in fetal development. Semin Cell Dev Biol 2011; 22: 619–23.
13. Venkatramanan S., Armata I.E., Strupp B.J., Finkelstein J.L. Vitamin B12 and Cognition in Children. Adv Nutr 2016 Sep; 7 (5): 879–88.
14. Chalouhi C., Faesch S., Anthoine-Milhomme M.-C., Fulla Y., Dulac O., Chéron G. Neurological consequences of vitamin B12 deficiency and its treatment. Pediatr Emerg Care 2008; 24: 538–41.
15. Graham S.M., Arvela O.M., Wise G.A. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 1992; 121 (Pt 1): 710–4.
16. Black M.M. Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull 2008; 29: S126–31.
17. Kuhne T., Bubl R., Baumgartner R. Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency. Eur J Pediatr 1991; 150: 205–8.
18. Wighton M.C., Manson J.I., Speed I., Robertson E., Chapman E. Brain damage in infancy and dietary vitamin B12 deficiency. Med J Aust 1979; 2: 1–3.
19. von Schenck U., 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.
20. Korenke G.C., Hunneman D.H., Eber S., Hanefeld F. Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature. Eur J Pediatr 2004; 163 (4–5): 196–201.
21. Diagnosis and treatment of vitamin B12 deficiency. An update. Haematologica 2006; 91: 1506–12.
22. Trakadis Y.J., Alfares A., Bodamer O.A., Buyukavci M., Christodoulou J., Connor P., et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis 2014 May; 37 (3): 461–73.
23. Carrillo N., Adams D., Venditti C.P. Disorders of Intracellular Cobalamin Metabolism. Initial Posting: February 25, 2008. Last Update: November 21, 2013. GeneReviews Advanced Search.
24. Kocaoglu C., Akin F., Caksen H., Böke S.B., Arslan S., Aygün S. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother. J Health Popul Nutr 2014 Jun; 32 (2): 367–71.
25. Codazzi D., Sala F., Parini R., Langer M. Coma and respiratory failure in a child with severe vitamin B 12 deficiency. Pediatr Crit Care Med 2005 Jul; 6 (4): 483–5.
26. Renault F., Verstichel P., Ploussard J.P., Costil J. Neuropathy in two cobalamin-deficient breast-fed infants of vegetarian mothers. Muscle Nerve 1999 Feb; 22 (2): 252–4.
27. Gambon R.C., Lentze M.J., Rossi E.Megaloblastic anaemia in one of monozygous twins breast-fed by their vegetarian mother. Eur J Pediatr 1986 Dec; 145 (6): 570–1.
28. Ciani F., Poggi G.M., Pasquini E., Donati M.A., Zammarchi E. Prolonged exclusive breastfeeding from vegan mother causing an acute onset of isolated methylmalonic aciduria due to a mild mutase deficiency. Clin Nutr 2000 Apr; 19 (2): 137–9.
29. From the Centers for Disease Control and Prevention. Neurologic impairment in children associated with maternal dietary deficiency of cobalamin – Georgia, 2001. JAMA 2003 Feb 26; 289 (8): 979–80.
30. Unal S., Rupar T., Yetgin S., Yarali N., Dursun A., Gursel T., et al. Transcobalamin II Deficiency in Four Cases with Novel Mutations. Turkish Journal of Hematology 2015; 32: 317–22.
Pediatric Hematology/Oncology and Immunopathology. 2019; 18: 70-77
Vitamin B12-deficiency anemia in infants: clinical presentation, current diagnostic and treatment
https://doi.org/10.24287/1726-1708-2019-18-3-70-77Abstract
Vitamin B12 (cobalamin) deficiency in infants exclusively breastfed is usually the result of its deficiency in the mothers (vegetarians or in the presence of unrecognized pernicious anemia or malabsorption syndrome). Cobalamin is crucial for the normal development of the nervous system, the production of erythrocytes and the synthesis of DNA. The classic manifestation of its deficiency is megaloblastic anemia and, in advanced cases, pancytopenia. However, infants often present neurological symptoms (fatigue, failure to thrive, regress of developmental skills, lethargy, motor disorders), as a consequence of inadequate myelination of the brain. Cobalamin treatment is effective in the most children, however, the neurological deficit varying degrees may persist. The long-term prognosis depends on overall duration of vitamin B12 deficiency and severity of symptoms. The article presents our own interesting clinical observations. Parents gave their permission for using personal data for clinical research and publications.
References
1. Kliegman R.M., Stanton B.F., St. Geme J.W., 3rd, Schor N.F., Behrman R.E. Vitamin B12 (Cobalamin). In: Sachdev HPS, Shah D, editors; Nelson textbook of pediatrics. 19th ed. Philadelphia, PA: Saunders; 2011; pp. 197–8.
2. Schrier S.L. Hematology ASH, and the anemia of the aged. Blood 2005; 106 (10): 3341–2.
3. de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008; 29: S238–44.
4. Karaoglu L., Pehlivan E., Egri M., Deprem C., Gunes G., Genc M., et al. Research article The prevalence of nutritional anemia in pregnancy in an east Anatolian province, Turkey. BMC Public Health 2010; 10: 329.
5. Oh R.C., Brown D.L. Vitamin B12 Deficiency Am Fam Physician 2003 Mar 1; 67 (5): 979–86.
6. Rasmussen S.A., Fernhoff P.M., Scanlon K.S. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001; 138: 10–7.
7. Allen L.H. Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol 1994; 352: 173–86.
8. Bjørke Monsen A.L., Ueland P.M., Vollset S.E., Guttormsen A.B., Markestad T., Solheim E., et al. Determinants of cobalamin status in newborns. Pediatrics 2001; 108: 624–30.
9. Rumyantsev A.G., Maschan A.A., Demikhov V.G., Skobin V.B., Zhurina O.N. Fede-ral'nye klinicheskie rekomendatsii po diagnostike i lecheniyu anemii, obuslovlennoi defitsitom V12. – M., 2015.
10. Molloy A.M., Kirke P.N., Brody L.C., Scott J.M., Mills J.L. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 2008; 29 (2 Suppl): S101–11; discussion S12–5.
11. Dror D.K., Allen L.H. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev 2008; 66 (5): 250–5.
12. Pepper M.R., Black M.M. B12 in fetal development. Semin Cell Dev Biol 2011; 22: 619–23.
13. Venkatramanan S., Armata I.E., Strupp B.J., Finkelstein J.L. Vitamin B12 and Cognition in Children. Adv Nutr 2016 Sep; 7 (5): 879–88.
14. Chalouhi C., Faesch S., Anthoine-Milhomme M.-C., Fulla Y., Dulac O., Chéron G. Neurological consequences of vitamin B12 deficiency and its treatment. Pediatr Emerg Care 2008; 24: 538–41.
15. Graham S.M., Arvela O.M., Wise G.A. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 1992; 121 (Pt 1): 710–4.
16. Black M.M. Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull 2008; 29: S126–31.
17. Kuhne T., Bubl R., Baumgartner R. Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency. Eur J Pediatr 1991; 150: 205–8.
18. Wighton M.C., Manson J.I., Speed I., Robertson E., Chapman E. Brain damage in infancy and dietary vitamin B12 deficiency. Med J Aust 1979; 2: 1–3.
19. von Schenck U., 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.
20. Korenke G.C., Hunneman D.H., Eber S., Hanefeld F. Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature. Eur J Pediatr 2004; 163 (4–5): 196–201.
21. Diagnosis and treatment of vitamin B12 deficiency. An update. Haematologica 2006; 91: 1506–12.
22. Trakadis Y.J., Alfares A., Bodamer O.A., Buyukavci M., Christodoulou J., Connor P., et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis 2014 May; 37 (3): 461–73.
23. Carrillo N., Adams D., Venditti C.P. Disorders of Intracellular Cobalamin Metabolism. Initial Posting: February 25, 2008. Last Update: November 21, 2013. GeneReviews Advanced Search.
24. Kocaoglu C., Akin F., Caksen H., Böke S.B., Arslan S., Aygün S. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother. J Health Popul Nutr 2014 Jun; 32 (2): 367–71.
25. Codazzi D., Sala F., Parini R., Langer M. Coma and respiratory failure in a child with severe vitamin B 12 deficiency. Pediatr Crit Care Med 2005 Jul; 6 (4): 483–5.
26. Renault F., Verstichel P., Ploussard J.P., Costil J. Neuropathy in two cobalamin-deficient breast-fed infants of vegetarian mothers. Muscle Nerve 1999 Feb; 22 (2): 252–4.
27. Gambon R.C., Lentze M.J., Rossi E.Megaloblastic anaemia in one of monozygous twins breast-fed by their vegetarian mother. Eur J Pediatr 1986 Dec; 145 (6): 570–1.
28. Ciani F., Poggi G.M., Pasquini E., Donati M.A., Zammarchi E. Prolonged exclusive breastfeeding from vegan mother causing an acute onset of isolated methylmalonic aciduria due to a mild mutase deficiency. Clin Nutr 2000 Apr; 19 (2): 137–9.
29. From the Centers for Disease Control and Prevention. Neurologic impairment in children associated with maternal dietary deficiency of cobalamin – Georgia, 2001. JAMA 2003 Feb 26; 289 (8): 979–80.
30. Unal S., Rupar T., Yetgin S., Yarali N., Dursun A., Gursel T., et al. Transcobalamin II Deficiency in Four Cases with Novel Mutations. Turkish Journal of Hematology 2015; 32: 317–22.
