Document Type : original article


1 M.D, Fellowship of Pediatric Endocrinology & Metabolism, Department of Pediatrics, School of Medicine, Akbar Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Mashhad University of medical sciences

3 Clinical Research Development Center, Akbar Hospital, Faculty of Medicine, Mashhad University of medical sciences, Mashhad, Iran

4 nursing and midwifery school, Mashhad University of Medical Sciences, Mashhad, Iran

5 Clinical Research Development Unit of Akbar Hospital ,Faculty of Medicine , Mashhad University of Medical Sciences, Mashhad, Iran

6 mashhad university of medicine ,pediatric endocrinology department


Background: Methylmalonic acidemia is a rare autosomal recessive disease in which there is a deficiency of intracellular cobalamin. This study aimed to assess the effectiveness of parenteral hydroxylcobalamin in the treatment of children with methylmalonic acidemia.
Method: This is a quasi-experimental study without a control group. The participants included under-18-year-old children with confirmed methylmalonic acidemia. There were only 17 patients with the inclusion criteria, all of whom were included in the study. They received 1mg hydroxylcobalamin injection for 3 or 7 days based on their clinical status. Data was gathered by a demographic questionnaire, along with laboratory tests of urine-MMA, and plasma homocysteine, measured before and after the intervention. Data analyses were performed using SPSS v. 26.
Results: The samples included 17 patients, most of whom were males (52.9%). They had various clinical manifestations consisting of hypotonia, seizure, verbal disorders, movement disorders, organomegaly, hematologic disorders, and ophthalmic disorders. The parenteral hydroxylcobalamin had a borderline significant effect on urine-MMA (p=0.05); this seems to be due to the sample shortage and can become strongly significant with sample increase.
Conclusion: The results revealed the effectiveness of parenteral hydroxylcobalamin in MMA patients. However, there is no standard guideline to suggest the perfect dose of it to acquire the optimum result; so it is suggested to conduct more clinical trials or cohort studies to be done.


  1. Eshraghi P. A methylmalonic acidemia case presenting with acrodermatitis enteropathica. International Journal of Pediatrics. 2014; 2(3.2):73-6.
  2. Sarah E Sheppard, Can Ficicioglu. Methylmalonic acidemia. Uptodate; 2023. Contract No.: 22/01/2023.
  3. Acquaviva C, Benoist JF, Pereira S, Callebaut I, Koskas T, Porquet D, Elion J. Molecular basis of methylmalonyl‐CoA mutase apoenzyme defect in 40 European patients affected by mut° and mut–forms of methylmalonic acidemia: Identification of 29 novel mutations in the MUT gene. Human mutation. 2005; 25(2):167-76.
  4. Carrillo-Carrasco N, Sloan J, Valle D, Hamosh A, Venditti C. Hydroxocobalamin dose escalation improves metabolic control in cblC. Journal of inherited metabolic disease. 2009; 32(6):728-31.
  5. Zhang C, Wang X, Hao S, Zhang Q, Zheng L, Zhou B, Liu F, Feng X, Chen X, Ma P, Chen C, Cao Z, Ma X. Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia. Scientific reports. 2020; 10(1):1-7.
  6. Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. Journal of the American Geriatrics Society. 2002; 50(11):1789-95.
  7. Tanpaiboon P. Methylmalonic acidemia (MMA). Molecular genetics and metabolism. 2005; 85(1):2-6.
  8. Willard HF, Rosenberg LE. Inherited methylmalonyl CoA mutase apoenzyme deficiency in human fibroblasts: evidence for allelic heterogeneity, genetic compounds, and codominant expression. The Journal of Clinical Investigation. 1980; 65(3):690-8.
  9. Zschocke J, Hoffman GF. Vademecum Metabolicum: Diagnosis and Treatment of Inborn Errors of Metabolism. 5th ed: Thieme; 2021 January 13, 2021.
  10. Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, Huemer M, Hochuli M, Assoun M, Ballhausen D, Burlina A, Fowler B, Grünert SC, Grünewald S, Honzik T, Merinero B, Pérez-Cerdá C, Scholl-Bürgi S, Skovby F, Wijburg F, MacDonald A, Martinelli D, Oliver Sass J, Valayannopoulos V, Chakrapani A. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet journal of rare diseases. 2014; 9(1):1-36.
  11. Fowler B, Leonard J, Baumgartner M. Causes of and diagnostic approach to methylmalonic acidurias. Journal of Inherited Metabolic Disease: Official Journal of the Society for the Study of Inborn Errors of Metabolism. 2008; 31(3):350-60.
  12. Yu Y, Shuai R, Liang L, Qiu W, Shen L, Wu S, Wei H, Chen Y, Yang C, Xu P, Chen X, Zou H, Feng J, Niu T, Hu H, Ye J, Zhang H, Lu D, Gong Z, Zhan X, Ji W, Gu X, Han L. Different mutations in the MMUT gene are associated with the effect of vitamin B12 in a cohort of 266 Chinese patients with mut‐type methylmalonic acidemia: A retrospective study. Molecular Genetics & Genomic Medicine. 2021; 9(11):e1822.
  13. Bartholomew DW, Batshaw ML, Allen RH, Roe CR, Rosenblatt D, Valle DL, Francomano CA. Therapeutic approaches to cobalamin-C methylmalonic acidemia and homocystinuria. The Journal of pediatrics. 1988; 112(1):32-9.
  14. Brox-Torrecilla N, Arhip L, Miguélez-González M, Castellano-Gasch S, Contreras-Chicote A, Rodríguez-Ferrero ML, et al. Late-onset methylmalonic acidemia and homocysteinemia. Nutricion hospitalaria. 2021; 38(4):871-5.
  15. Obeid R, Fedosov SN, Nexo E. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Molecular nutrition & food research. 2015; 59(7):1364-72.