Clinical and biochemical footprints of inherited metabolic diseases. XII. Immunological defects

Boer, Lonneke de; Cambi, Alessandra; Verhagen, Lilly M.; Haas, Paola de; Karnebeek, Clara D.M. van; Blau, Nenad; Ferreira, Carlos R.

doi:10.1016/j.ymgme.2023.107582

Cited by 6 publications

(3 citation statements)

References 78 publications

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“…In general, more than 170 types of IEMs are accompanied by immunological manifestations ranging from abnormal immune cell counts, autoimmunity, and autoinflammation to recurrent infections, among which T/B lymphocytes, macrophages, and neutrophils are the most affected cell types in IEMs accompanied by immune disorders (de Boer et al., 2023 ). Treatment and management of immune phenotypes are highly important for treating IEMs (Francisco et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2

Fan,

Wu,

Wang

et al. 2024

Molec Gen & Gen Med

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BackgroundCongenital disorders of glycosylation (CDG) are a type of inborn error of metabolism (IEM) resulting from defects in glycan synthesis or failed attachment of glycans to proteins or lipids. One rare type of CDG is caused by homozygous or compound heterozygous loss‐of‐function variants in mannosidase alpha class 2B member 2 (MAN2B2). To date, only two cases of MAN2B2‐CDG have been reported worldwide.MethodsTrio whole‐exome sequencing (Trio‐WES) was conducted to screen for candidate variants. N‐glycan profiles were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). MAN2B2 expression was evaluated by western blotting. MX dynamin like GTPase 1 (MX1) function was estimated via Thogoto virus (THOV) minireplicon assay.ResultsTrio‐WES identified compound heterozygous MAN2B2 (hg19, NM_015274.1) variants (c.384G>T; c.926T>A) in a CDG patient. This patient exhibited metabolic abnormalities, symptoms of digestive tract dysfunction, infection, dehydration, and seizures. Novel immune dysregulation characterized by abnormal lymphocytes and immunoglobulin was observed. The MAN2B2 protein level was not affected, while LC–MS/MS showed obvious disruption of N‐glycans and N‐linked glycoproteins.ConclusionWe described a CDG patient with novel phenotypes and disruptive N‐glycan profiling caused by compound heterozygous MAN2B2 variants (c.384G>T; c.926T>A). Our findings broadened both the genetic and clinical spectra of CDG.

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Section: Discussionmentioning

confidence: 99%

Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2

Fan,

Wu,

Wang

et al. 2024

Molec Gen & Gen Med

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“…The interplay between infections and the immunological status of patients with IEMs must be fully explained [ 8 ]. Although immunological complications are becoming increasingly prevalent due to numerous inborn errors of metabolism (IEMs), their characteristics and mechanisms are poorly known [ 11 ]. Thus, the main goal of this study was to explore the serum levels of immunoglobulins and hematological parameters in PD patients during metabolic compensation and decompensation states.…”

Section: Introductionmentioning

confidence: 99%

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

López-Mejía,

Vela-Amieva,

Guillén-López

et al. 2024

Nutrients

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Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).

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“…Although not systematically examined, all the above result in greater morbidity, prolonged hospital stays and a worsening outcome in a number of IMDs [6,7].…”

Section: Introductionmentioning

confidence: 99%

The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

Tummolo,

Melpignano

2023

Microorganisms

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Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). The basic molecular mechanisms behind the role of infections in these conditions have not been completely clarified. This review points out the different mechanisms behind the relationship between IMDs and infections, providing an overview of this still-under-investigated area. Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. In addition, a dietary regimen with a reduced intake of both micro- and macronutrients can potentially compromise the ability of the immune system to deal with an infection. There is recent pre-clinical evidence showing that during infections there may be a disruption of substrates of various metabolic pathways, leading to further cellular metabolic alteration. Therefore, infective agents may affect cellular metabolic pathways, by mediation or not of an altered immune system. The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.

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Clinical and biochemical footprints of inherited metabolic diseases. XII. Immunological defects

Cited by 6 publications

References 78 publications

Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2

Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2

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

The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

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