Evaluation of Complete Blood Count Parameters in Patients with Methylmalonic Acidemia

Öz

Objective: We aimed to evaluate the frequency of pathological changes in blood parameters and their relationship with serum creatinine and glomerular filtration rate (GFR) in patients with methylmalonic acidemia. Methods: Demographic and laboratory data of 46 patients diagnosed by acylcarnitine, urine organic acid, and/or molecular analyses for methylmalonic acidemia were evaluated. In all patients, complete blood counts, serum iron concentrations, serum iron-binding capacity, vitamin B12 and folate concentrations, and serum creatinine tests were performed during the period when the patients were metabolically stable. Results: Among the 46 patients with anaemia, 54.3% had anaemia of chronic disease, 19.6% had iron deficiency anaemia. Bicytopenia was detected in 17.4%. There was a negative correlation between serum creatinine levels and leucocyte, lymphocyte, erythrocyte, and platelet counts. GFR values were positively correlated with haemoglobin value, leukocyte, lymphocyte, erythrocyte, and platelet counts. Conclusions: The presence of anaemia, neutropenia, thrombocytopenia, and erythrocyte volume changes in patients with methylmalonic acidemia apart from the metabolic attack period is a situation that reveals the necessity of a detailed nutritional evaluation of patients. Evaluation of renal function in the presence of haematological complications and taking precautions if signs of renal failure are noted may prevent worsening of complications.

Anahtar Kelimeler

• Methylmalonic acidemia
• anemia
• thrombocytopenia
• renal failure
• bone marrow

Kaynakça

1. Dionisi-Vici C, Deodato F, Röschinger W, Rhead W, Wilcken B. Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006;29(2-3):383-9. google scholar
2. Zwickler T, Haege G, Riderer A, Hörster F, Hoffmann GF, Burgard P et al. Metabolic decompensation in methylmalonic aciduria: which biochemical parameters are discriminative? J Inherit Metab Dis. 2012;35(5):797-806. google scholar
3. Morath MA, Hörster F, Sauer SW. Renal dysfunction in methylmalonic acidurias: review for the paediatric nephrologist. Pediatr Nephrol. 2013;28(2):227-35. google scholar
4. Hörster F, Baumgartner MR, Viardot C, Suormala T, Burgard P, Fowler B, et al. Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB). Pediatr Res. 2007;62(2):225-30. google scholar
5. Mikhail A, Brown C, Williams JA, Mathrani V, Shrivastava R, Evans J et al. Renal association clinical practise guideline on Anaemia of Chronic Kidney Disease. BMC Nephron. 2017;18(1):345. google scholar
6. Inoue S, Krieger I, Sarnaik A, Ravindranath Y, Fracassa M, Ottenbreit MJ. Inhibition of bone marrow stem cell growth in vitro by methylmalonic acid: a mechanism of pancytopenia in patients with methylmalonic acidemia. Pediatr Res. 1981;15(2):95-8. google scholar
7. Orkin SH ND, Ginsburg D, Look AT, Fisher DE, Lux S. Nathan and Oski’s haematology of infancy and childhood. 8th ed. Philadelphia: Saunders; 2015. google scholar
8. WHO, UNICEF, UNU. Guideline: daily iron supplementation in infants and children. 2016 google scholar

9. Auerbach M, Adamson JW. How to diagnose and treat iron deficiency anaemia. Am J Hematol. 2016;91(1):31-8. google scholar
10. Ezekowitz, R.A.S.J. Haematologic manifestations of systemic diseases. In: Nathan DG OS, Ginsburg D, Look AT. Haematology of Infancy and Childhood. Philadelphia: W. B. Saunders; 2003. p. 1771-2. google scholar
11. Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet. 2017;389(10075):1238-52. google scholar
12. Chandler RJ, Zerfas PM, Shanske S, Sloan J, Hoffmann V, DiMauro S et al. Mitochondrial dysfunction in mut methylmalonic acidemia. Faseb j. 2009;23(4):1252-61. google scholar
13. Kölker S, Burgard P, Sauer SW, Okun JG. Current concepts in organic aciduria: understanding intra- and extracerebral disease manifestation. J Inherit Metab Dis. 2013;36(4):635-44. google scholar
14. Kölker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, et al. Phenotypic spectrum of organic aciduria and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015;38(6):1059-74. google scholar
15. He R, Mo R, Shen M, Kang L, Song J, Liu Y et al. Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long-term follow-up in a large cohort of cases. Orphanet J Rare Dis. 2020;15(1):200. google scholar
16. Matsui SM, Mahoney MJ, Rosenberg LE. Natural history of the inherited methylmalonic acidemias. N Engl J Med. 1983;308(15):857-61. google scholar
17. Tavil B, Sivri HS, Coskun T, Gurgey A, Ozyurek E, Dursun A et al. Haematological findings in children with inborn errors of metabolism. J Inherit Metab Dis. 2006;29(5):607-11. google scholar
18. Bakshi NA, Al-Anzi T, Mohamed SY, Rahbeeni Z, AlSayed M, Al-Owain M et al. Spectrum of bone marrow pathology and haematological abnormalities in methylmalonic acidemia. Am J Med Genet A. 2018;176(3):687-91. google scholar
19. Santos EW, Oliveira DC, Silva GB, Tsujita M, Beltran JO, Hastreiter A et al. Haematological alterations in protein malnutrition. Nutr Rev. 2017;75(11):909-19. google scholar
20. Daly A, Evans S, Gerrard A, Santra S, Vijay S, MacDonald A. Nutritional Intake of Patients with Organic Acidemia on Enteral Tube Feeding: Can We Do Better? JIMD Rep. 2016;28:29-39. google scholar