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

Abstract

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.

Hypogammaglobulinemia Class G Is Present in Compensated and Decompensated Patients with Propionate Defects, Independent of Their Nutritional Status

“…A previous study found that the absolute lymphocyte subset counts were low in 91% of PD patients, with CD4+ T-cell lymphopenia being the most common. We also found that 81% of patients presented a low CD4+/CD8+ T-cell ratio [ 19 ]. Our study corroborates the findings of other authors who reported that PD patients are prone to hypogammaglobulinemia class G [ 14 , 15 , 16 , 17 , 18 ].…”

BNT162b2 COVID-19 vaccination elicited protective robust immune responses in pediatric patients with inborn errors of metabolism

“…Organic acidemia (OA) is the most studied subtype of IEM in terms of secondary immunodeficiency, and it has been suggested that it may result from pancytopenia and/or neutropenia, presumably due to bone marrow suppression by precursory toxic metabolites ( 19 , 20 ). Hypogammaglobulinemia, depletion of B and/or T-cells, and lack of memory B cell formation despite normal B cell count have also been described even in nonacute phases of the disease ( 12 , 19 , 21 – 24 ). In lysinuric protein intolerance (LPI), most patients tended to have subnormal IgG subclasses, whereas serum IgG, IgM, and IgA levels were between reference ranges in most patients ( 11 ).…”