B 12 [ ] gas chromatography-mass spectrometry, GC-MS B 12 B B 12 B 12 B 12 [ ] B 12 - GC

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2 B 12 [ ] gas chromatography-mass spectrometry, GC-MS B 12 B B 12 B 12 B 12 [ ] B 12 - GC-MS 1

3 The diagnosis and treatment of the patients with secondary methylmalonic aciduria due to maternal vitamin B 12 deficiency Postgraduate: Qian Ning Tutor: Yang Yanling Department of Pediatrics, Peking University First Hospital [Abstract] Objectives: To study the cause, diagnosis and treatment of the patients with secondary methylmalonic aciduria due to maternal vitamin B 12 deficiency. Methods: 7 patients (5 boys and 2 girls) with secondary methylmalonic aciduria were reviewed. Their urine organic acids were analyzed by gas chromatography-mass spectrometry (GC-MS). The mothers healthy and nutritional conditions, serum cobalamin, folic acid and homocystine concentration were further investigated retrospectively. All patients were treated by vitamin B 12 and folic acid supplementations. Results: Case 1 and 2 were hospitalized at the age of first day because of jaundice. One sibling of case 1 died in neonatal respiratory distress at the 5 th day of life. Cases 3 and 4 were twin brothers. They showed lethargy poor feeding, vomiting after birth and had seizures at the age of two month and four month, respectively. Cases 5-7 were breast fed babies. They were hospitalized at the age of 2 to 13 months because of vomiting, seizures or mental retardation. Varied anemia was found in 6 patients. Among them three cases had megaloblastic anemia. One case presented progressive hemolytic anemia. Five patients had metabolic acidosis and liver dysfunction. Methylmalonic aciduria was found in all of the patients. Four mothers of the patients had chronic gastritis. One had gallstones in liver and gallbladder. One was a strict vegetarian for over 10 years. Decreased serum vitamin B 12, folic acid and elevated homocystine concentrations were found in the mothers of the patients. After the supplement of vitamin B 12 and folic acid, significant 2

4 improvement was observed in all patients. 6 cases showed normal development, while mild mental retardation still remained in 1 boy because of delayed diagnosis. Conclusions: Chronic gastritis, liver/gall disease or strict vegetarian diet might lead to maternal vitamin B 12 deficiency and result in infantile secondary methylmalonic aciduria. Early diagnosis and vitamin B 12 and folic acid supplements are the key points to improve the prognosis of the patients. Maternal healthy investigation, serum vitamin B 12, folic acid and homocystine analysis should be considered for the infant patients with anemia, neurological symptoms and methylmalonic aciduria as the deferential diagnosis. [Key words] Vitamin B 12, Folic acid, Homocystine, Methylmalonic Aciduria, Gas chromatography/mass spectrometry (GC/MS) 3

5 methylmalonic aciduria methylmalonic acidemia [1, 2] 1967 [3,4] A (mutase apoenzyme) B 12, vitamin B 12 A 6q , (complete mutase deficiency) mut 0 (partial mutase deficiency) mut - 5 (AdoCbl) (mitochondrial Cbl reductase, CblA) (mitochodrial cobalamin adenosyltransferase, CblB) 3 (MeCbl) (CblC CblD CblF) mut 0 mut - CblA CblB CblC CblD CblF (homocystinemia) [1,2,9] B 12 B 12 [1,2,10] 12 Cb1A CblC CblD CblF B 12 Cb1B B 12 B 12 [1,2,9] B 12 [2,11-13] 4

6 B 12 B 12 [2] 173 B 12 B 12 [14] A A B 12 [1,2,9] A [1,2,15] [16], [17,18] 1. mut 0 80% [1,2,9] mut 0 Cb1A Cb1B 1 Cb1C Cb1D [1,2,9] Cb1F [19,20] 2. 5

7 [1,2,10] 3. [1,2,10] [21-23] [24-26] [1,2,27] [2,28] 4. [1,2,10] B 12 [29] [2,9,10] [2,30,31] [2,32] Goodman Cb1D 14 2 [2,33] 5. CT MRI [2,34] 6

8 [2,35] [36] - <2 mmol /Mol 24 <5mg mmol /Mol mg µmol/l [37] [2,9,10] [1,2,9] [1,38,39] [2,40] [1,2,10] 7

9 B [2,9,10,41] 12 B 12 B 12 1 mg d 3 5d, B 12 B 12 B 12 [10,42,43] B ~1.2g/kg B 12 B 12 1mg 10~20mg [2,10,44] [2,10,45] mg/d mg/d [2,9,10] (betaine) mg/d [2,9,46] MUT 0 B 12 [1,2,9] Cb1A 25 B 12 4 B [47,48] [1,2,48] 8

10 B 12 - gas chromatography-mass spectrometry, GC-MS [2,10,46] B 12 vitamin B 12 B 12 [2,49] d 13M gas chromatography-mass spectrometry, GC-MS 9

11 CT MRI B 12 7 B µg/d 3d 500 µg/d 5 mg/d 1 6 [2,10,44] d ph HCO mmol/l Hb 145g/L MCV 110 fl d Hb 200 g/l 3d 8d Hb 51 g/l 13.7% 338 µmol/l 3 4 3d 4 2 Hb g/l ALT IU/L AST IU/L HCO mmol/l µmol/l 10

12 CT Hb g/l ALT IU/L AST IU/L HCO mmol/l 84 µmol/l Hb 115 g/l MCV fl ALT 56 IU/L AST 62 IU/L HCO mmol/l 263 µmol/l CT 2 6 B 12 B 12 2 B mmol/mol. <2 - [1,2,9] 2. B d Hb

13 70 80 g/l [45] 1 7 B pmol/l pmol/l nmol/l >6.8 nmol/l mmol/l mmol/l B 12 7 A B 12 [2,9,10] A A A [2,9,46] [10,48,49] GC MS B 12 [2,50,51] B 12 [51-53] B 12 transcobalamin II TC DNA 12

14 [2,51,54] MeB 12 AdoB 12 MeB 12 AdoB 12 A A A A [55] B 12 B 12 [45,51,57] 4 B 12 [2,58] [2,59,60] B 12 B 12 Bonny L Specker B pmol/l pmol/l B 12 B 12 B 12 < 362 pmol/l [61-63] Bonny L Specker mmol/mol mmol/mol B 12 B 12 [64] 3 4 H 2 C B 12 [65-67] 4 1 B

15 B B 12 B 12 B 12 50% B 12 B 12 B [68,69] [2,9,10] B 12 B 12 B A (mutase apoenzyme) 14

16 B 12, vitamin B 12 - B 12 B 12 B 12 B 12 - B B 12 B Wayne A. Fenton, Roy A. Gravel, David S. Rosenblatt. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D. The metabolic and molecular basis of inherited diseases, 8 th ed. McGraw-Hill, New York, 2001: William L Nyhan, Pinar T. Ozand. Methylmalonic acidemia. In: Atlas of metabolic diseases. Chapman & Hall Medical. Spain, 1998: Oberholzer, v.g. Levin, B. Burgess, E.A, Young WF. Methylmalonic aciduria: an inborn error of metabolism leading to chronic metabolic acidosis. Arch Dis Child, 1967, 42:

by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (2

by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (2 论著临床研究 doi: 0.7499/j.issn.008-8830.204.2.007 郑州市城区儿童哮喘的流行病学调查及发病相关因素分析赵坤宋桂华古华倩 2 刘爽 3 张岩郭彦荣 (. 河南中医学院第一附属医院儿科医院, 河南郑州 450000; 2. 杭州市余杭区