Abnormalities in subsets of B and T cells in Mexican patients with inborn errors of propionate metabolism: observations from a single-center case series

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E.A. Medina-Torres
M Vela-Amieva
L Galindo-Campos
I Ibarra-González
S Espinosa-Padilla
S Guillén-López
L López-Mejía
C. Fernández-Lainez


immunodeficiency, inborn errors of metabolism, inherited metabolic disorders, methylmalonic acidemia, propionic acidemia.


Background: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hematological abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients.

Methods: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, biochemical, nutritional, hematological, and lymphocyte subsets were analyzed.

Results: Despite being considered clinically stable, 91% of patients had hematological or immunological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 studied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%).

Conclusion: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic com-plications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients.

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1. Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014;9:130. https://doi.org/10.1186/ s13023-014-0130-8

2. Pillai NR, Stroup BM, Poliner A, Rossetti L, Rawls B, Shayota BJ, et al. Liver transplantation in propionic and methylmalonic acidemia: A single center study with literature review. Mol Genet Metab. 2019;128(4):431–443. https://doi.org/10.1016/j. ymgme.2019.11.001

3. Stork LC, Ambruso DR, Wallner SF, Sambrano JE, Moscinski LC, Wilson HL, McCabe ER. Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro. Pediatr Res. 1986;20(8):783–8. https://doi. org/10.1203/00006450-198608000-00017

4. Haijes HA, Jans JJM, Tas SY, Verhoeven-Duif NM, van Hasselt PM. Pathophysiology of propionic and methylmalonic acidemias. Part 1: Complications. J Inherit Metab Dis. 2019;42(5):730–44. https://doi.org/10.1002/jimd.12129

5. 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 for pancytopenia in a patient with methylmalonic acidemia. Pediatr Res. 1981;15(2): 95–8. https://doi.org/10.1203/00006450-198102000-00001

6. Pena L, Burton BK. Survey of health status and complications among propionic acidemia patients. Am J Med Genet A. 2012;158A:1641–6. https://doi.org/10.1002/ajmg.a.35387

7. Al Essa M, Rahbeeni Z, Jumaah S, Joshi S, Al Jishi E, Rashed MS, et al. Infectious complications of propionic acidemia in Saudia Arabia. Clin Genet. 1998;54(1):90–4. https://doi. org/10.1111/j.1399-0004.1998.tb03702.x

8. Griffin TA, Hostoffer RW, Tserng KY, Lebovitz DJ, Hoppel CL, Mosser JL, et al. Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia. Acta Paediatr. 1996;85(7):875–8. https://doi.org/10.1111/j.1651-2227.1996. tb14172.x

9. Bakshi NA, Al-Anzi T, Mohamed SY, Rahbeeni Z, AlSayed M, Al-Owain M, Sulaiman RA. Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia. Am J Med Genet A. 2018;176(3):687–91. https://doi. org/10.1002/ajmg.a.38599

10. Ibarra-González I, Fernández-Lainez C, Reyes-González DI, Belmont-Martínez L, Guillén-López S, Monroy-Santoyo S, Vela-Amieva M. Inborn errors of intermediary metabolism in critically ill Mexican newborns. JIEMS. 2014;2:1–7. https://doi. org/10.1177/2326409814529649

11. Müller S, Falkenberg N, Mönch E, Jakobs C. Propionic acidaemia and immunodeficiency. Lancet. 1980;1(8167):551–2. https://doi.org/10.1016/S0140-6736(80)92815-9

12. Hohlstein P, Gussen H, Bartneck M, Warzecha KT, Roderburg C, Buendgens L, et al. Prognostic relevance of altered lymphocyte subpopulations in critical illness and sepsis. J Clin Med. 2019;8(3). pii: E353. https://doi.org/10.3390/jcm8030353

13. Rudilla F, Franco-Jarava C, Martínez-Gallo M, Garcia-Prat M, Martín-Nalda A, Rivière J, et al. Expanding the clinical and genetic spectra of primary immunodeficiency-related dis-orders with clinical exome sequencing: Expected and unexpected findings. Front Immunol. 2019;10:2325. https://doi. org/10.3389/fimmu.2019.02325