RESUMO
Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism, comprising over 160 described diseases to this day. CDG are characterized by a dysfunctional glycosylation process, with molecular defects localized in the cytosol, the endoplasmic reticulum, or the Golgi apparatus. Depending on the CDG, N-glycosylation, O-glycosylation and/or glycosaminoglycan synthesis can be affected. Various proteins, lipids, and glycosylphosphatidylinositol anchors bear glycan chains, with potential impacts on their folding, targeting, secretion, stability, and thus, functionality. Therefore, glycosylation defects can have diverse and serious clinical consequences. CDG patients often present with a non-specific, multisystemic syndrome including neurological involvement, growth delay, hepatopathy and coagulopathy. As CDG are rare diseases, and typically lack distinctive clinical signs, biochemical and genetic testing bear particularly important and complementary diagnostic roles. Here, after a brief introduction on glycosylation and CDG, we review historical and recent findings on CDG biomarkers and associated analytical techniques, with a particular emphasis on those with relevant use in the specialized clinical chemistry laboratory. We provide the reader with insights and methods which may help them properly assist the clinician in navigating the maze of glycosylation disorders.
Assuntos
Biomarcadores , Defeitos Congênitos da Glicosilação , Humanos , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/metabolismo , Defeitos Congênitos da Glicosilação/genética , Glicosilação , Biomarcadores/metabolismoRESUMO
PURPOSE: Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism. Despite the availability of next-generation sequencing techniques and advanced methods for evaluation of glycosylation, CDG screening mainly relies on the analysis of serum transferrin (Tf) by isoelectric focusing, HPLC or capillary electrophoresis. The main pitfall of this screening method is the presence of Tf protein variants within the general population. Although reports describe the role of Tf variants leading to falsely abnormal results, their significance in confounding diagnosis in patients with CDG has not been documented so far. Here, we describe two PMM2-CDG cases, in which Tf variants complicated the diagnostic. EXPERIMENTAL DESIGN: Glycosylation investigations included classical screening techniques (capillary electrophoresis, isoelectric focusing and HPLC of Tf) and various confirmation techniques (two-dimensional electrophoresis, western blot, N-glycome, UPLC-FLR/QTOF MS with Rapifluor). Tf variants were highlighted following neuraminidase treatment. Sequencing of PMM2 was performed. RESULTS: In both patients, Tf screening pointed to CDG-II, while second-line analyses pointed to CDG-I. Tf variants were found in both patients, explaining these discrepancies. PMM2 causative variants were identified in both patients. CONCLUSION AND CLINICAL RELEVANCE: We suggest that a neuraminidase treatment should be performed when a typical CDG Tf pattern is found upon initial screening analysis.
Assuntos
Defeitos Congênitos da Glicosilação , Fosfotransferases (Fosfomutases)/deficiência , Humanos , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/complicações , Transferrina/genética , Transferrina/metabolismo , Neuraminidase/metabolismo , GlicosilaçãoRESUMO
TMEM165-CDG has first been reported in 2012 and manganese supplementation was shown highly efficient in rescuing glycosylation in isogenic KO cells. The unreported homozygous missense c.928G>C; p.Ala310Pro variant leading to a functional but unstable protein was identified. This patient was diagnosed at 2 months and displays a predominant bone phenotype and combined defects in N-, O- and GAG glycosylation. We administered for the first time a combined D-Gal and Mn2+ therapy to the patient. This fully suppressed the N-; O- and GAG hypoglycosylation. There was also striking improvement in biochemical parameters and in gastrointestinal symptoms. This study offers exciting therapeutic perspectives for TMEM165-CDG.
Assuntos
Proteínas de Transporte de Cátions , Defeitos Congênitos da Glicosilação , Humanos , Manganês/metabolismo , Galactose , Antiporters/metabolismo , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/metabolismoRESUMO
BACKGROUND: Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. METHODS: We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. RESULTS: Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 µmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. CONCLUSION: Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.
Assuntos
COVID-19 , Hepcidinas , Humanos , Hepcidinas/metabolismo , Estudos de Coortes , Interleucina-6 , Ferro , Ferritinas , Transferrina/metabolismoRESUMO
Carbohydrate-deficient transferrin (CDT) is a performant biomarker used for the diagnosis of chronic alcohol abuse. Here, we describe the case of a 39-year-old male of Tamil ethnicity who had extremely elevated (20%) CDT using capillary electrophoresis (but without glycoforms profile analysis), putting his driving license regranting at risk. However, the patient had no symptoms of chronic alcohol abuse, normal mean corpuscular volume and gamma-glutamyl transferase, and did not admit to any alcohol consumption. Re-analysis by N-Latex CDT immunoassay revealed a CDT at 1.7%. Further investigation by whole-exome sequencing revealed a c.1295A>G missense variant at the heterozygous state on the TFgene. This variant is characterized by an amino-acid change at a consensus sequence forN-glycosylation. Therefore, half of the patient transferrin proteins were lacking a completeN-glycan chain out of two, despite no alcohol consumption. This also explains the discrepancies between the techniques, as the NLatex antibodies did not recognize the mutated sequence. In conclusion, this case highlights the importance of comparing laboratory results between themselves and the clinical description, the absolute requirement for glycoforms profile analysis before delivering results, and the necessity to confirm intriguing results by another technique in a specialized laboratory.
Assuntos
Alcoolismo , Masculino , Humanos , Adulto , Alcoolismo/diagnóstico , Alcoolismo/genética , Índia , Consumo de Bebidas Alcoólicas , Transferrina/análise , Biomarcadores/análiseRESUMO
Purpose: Measurement of the haemolysis index (HI) is usually performed in clinical chemistry laboratories in order to inform about whether biological analyses are influenced by in vivo or in vitro haemolysis of the specimen. Our aim was to evaluate the analytical performance of Abbott C-16000 analyser HI measurement in order to determine whether this could be used to reliably measure cell-free haemoglobin (fHB) in plasma samples. Methods: The repeatability, reproducibility, lower limit of detection (LLOD) and lower limit of quantification (LLOQ) of C-16000 HI measurement were determined as well as the potential interference of bilirubin, triglycerides and myoglobin. C-16000 HI values of biological samples with various ranges of fHB were compared to those measured using the established reference method, second-derivate spectroscopy. Results: Results: C-16000 HI determination showed excellent linear correlation with the reference method (y = 1.0043x 1.248, R² = 0.998), a broad analytical measurement range (400-20,000 mg/L; y = 0.9904x + 72.972, R² = 0.999), clinically relevant LLOD (56 mg/L) and LLOQ (84 mg/L), good repeatability (coefficient of variation (CV) = 1-15%) and good reproducibility (CV = 5-7%). No interference was observed with myoglobin at concentrations as high as 35,447 mg/L, unconjugated and conjugated bilirubin (at concentrations up to 500 mg/L and 375 mg/L, respectively) or triglycerides up to 6.8 mmol/L. However, a significant underestimation of fHB concentrations was observed at higher triglyceride levels. Conclusion: This study demonstrates that Abbott C-16000 analyser HI is reliable and accurately measures plasma fHB concentrations under pathophysiological conditions except when there are high blood concentrations of triglycerides.
Assuntos
Hemólise , Mioglobina , Humanos , Reprodutibilidade dos Testes , Hemoglobinas/análise , Bilirrubina , TriglicerídeosRESUMO
Herein, we report the case of a 42-year-old woman, hospitalized in a French tertiary hospital for a relapse of a chronic enteropathy, who was found on admission to have no detectable serum transferrin. Surprisingly, she only exhibited mild anaemia. This atransferrinemia persisted for two months throughout her hospitalization, during which her haemoglobin concentration remained broadly stable. Based on her clinical history and evolution, we concluded to an acquired atransferrinemia secondary to chronic undernutrition, inflammation and liver failure. We discuss the investigations performed in this patient, and hypotheses regarding the relative stability of her haemoglobin concentration despite the absence of detectable transferrin.
Assuntos
Erros Inatos do Metabolismo dos Metais , Transferrina , Humanos , Feminino , Adulto , Ferro , HemoglobinasRESUMO
Ventilator-associated pneumonia (VAP) is a frequent nosocomial infection in neonatal intensive care units (NICU). Extremely preterm infants are at highest risk of developing VAP. Several studies indicate that oral care included in a preventive protocol effectively reduces neonatal VAP incidence. We investigated the effects of oral care with breast milk on oral immune defenses and microbiota in extremely preterm infants. Thirty infants born ≤ 30 weeks gestation hospitalized at our NICU were selected and divided into three groups: oral care with breast milk, formula, or sterile water. Effects on oral immune defenses in vivo were studied using ELISA to measure lactoferrin (LF) and secretory immunoglobulin A (sIgA) in pharyngeal aspirates before and after oral care. Different LF concentrations were tested in vitro to assess their effects on loads of selected bacterial species by culture. Effects on selected bacteria potentially responsible for VAP in vivo were studied by real-time PCR detection in pharyngeal aspirates before and after oral care. Oral care with breast milk significantly increases LF concentrations to 69.8 × 103 ng/ml (p = 0.012) and sIgA to 36.8 × 103 ng/ml (p = 0.017) in vivo. These LF concentrations considerably reduce loads of E. coli, S. epidermidis, S. aureus, and P. aeruginosa, in vitro. However, contrary to our expectation, no effect on colonization of bacteria most commonly responsible for VAP was found in vivo. CONCLUSION: In extremely preterm infants, oral care with breast milk increases local immune defense markers (LF, sIgA), which combat bacterial infections. Further clinical trials should be conducted to evaluate their effects on VAP prevention in neonates. WHAT IS KNOWN: ⢠The population at higher risk to develop VAP are preterm infants. ⢠Several studies indicate oral care within a preventive bundle is effective in reducing neonatal VAP incidence. WHAT IS NEW: ⢠In extremely premature infants, oral care with breast milk causes a significant increase in local immune defences in terms of lactoferrin (LF) and secretory immunoglobulin A (sIgA). ⢠LF concentrations obtained after oral care with breast milk decreased loads of bacteria most commonly responsible for VAP in premature infants under experimental in-vitro.
Assuntos
Lactente Extremamente Prematuro , Leite Humano , Pneumonia Associada à Ventilação Mecânica , Feminino , Humanos , Recém-Nascido , Escherichia coli , Imunoglobulina A Secretora , Unidades de Terapia Intensiva Neonatal , Lactoferrina/análise , Leite Humano/química , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Staphylococcus aureusRESUMO
While considerable efforts have been accomplished to standardize the measurement of plasma creatinine (PCr), urine creatinine (UCr) has not been subject to the same scrutiny. UCr is importantly used when measuring biomarkers in spot urines, to assess urine output and variable dilution of urine samples. Here, we report underestimation of Jaffe UCr measurements on the Siemens Dimension Vista® analyzer, critically affecting samples with UCr ≤2 mmol/L. We demonstrate that this error is caused by automatic urine pre-dilution by the Vista's «urine mode¼, and that UCr measured in «plasma mode¼ without pre-dilution does not present this error. In the absence of a comprehensive solution proposed by Siemens, we propose simple formulae that can be easily implemented in a laboratory to correct these low UCr measurements. Importantly, the observed UCr underestimation can significantly influence reported results for biomarkers/UCr ratios measured in spot urine. Indeed, these results can be overestimated up to +84.4 % before correction using our formulae. This can sometimes lead to misclassification according to clinical thresholds, e.g. Kidney disease: improving global outcomes (KDIGO) guidelines for urine albumin/creatinine. This highlights the need for every clinical laboratory to assess the detection limits of their assays, including for lesser-discussed parameters such as UCr. Indeed, the error we reported here may affect other urine assays performing systematic urine pre-dilution and could have significant repercussions on the clinical management of patients.
Assuntos
Laboratórios Clínicos , Urinálise , Humanos , Creatinina , Testes de Função Renal , Biomarcadores/urinaRESUMO
Herein, we described the case of a newborn male, from consanguineous parents, who developed, at day 11 of life, an obstructive hydrocephalus resulting from bilateral cerebellar hemorrhage without evident cause. Then, at 1 month, he developed a fulminant hepatitis with hyperammonia, hyperlactatemia and metabolic acidosis. Infectious and first line metabolic explorations were normal. Screening for congenital disorder of glycosylation (CDG) was performed using capillary electrophoresis and western blot of serum transferrin. Abnormal results were evocative of mannose-phosphate isomerase deficiency (MPI-CDG or CDG-Ib) as it can be responsible for fulminant hepatitis, digestive disease, developmental delay, and coagulopathy. However, trio whole exome sequencing revealed a pathogenic variant at the homozygous state in ALDOB, responsible for hereditary fructose intolerance (HFI), an inherited metabolic disorder with excellent prognosis under a fructose-free diet. HFI had not been previously evoked in view of the absence of diet diversification, but meticulous inquiry revealed that parents systematically added white sugar to the bottle milk of their child, unintentionally triggering potentially fatal HFI decompensations. Early genetic analysis upsetted both diagnosis and prognosis for this infant who had excellent development after fructose removal. This full-of-surprises diagnostic approach illustrates the importance of an integrative collaboration between clinicians, biochemists, and geneticists.
Assuntos
Defeitos Congênitos da Glicosilação , Intolerância à Frutose , Necrose Hepática Massiva , Lactente , Criança , Recém-Nascido , Humanos , Masculino , Glicosilação , Intolerância à Frutose/diagnóstico , Intolerância à Frutose/genética , Intolerância à Frutose/metabolismo , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Erros de DiagnósticoRESUMO
Alanine (ALT) and aspartate aminotransferases (AST) are intracellular enzymes involved in the metabolism of amino acids. The measurements of their activities are two of the most ordered tests in clinical laboratories, used to screen, diagnose and follow diseases affecting the liver. Recent works highlighted that reference values for ALT and AST vary according to the analytical method and the individual's characteristics, like with many other biomarkers. Reference values for ALT show clinically significant differences according to the analytical method (higher when supplementing samples with phosphate pyridoxal), gender (higher in males than in females), body mass index (positive correlation), and age (higher in infants and the elderly), but not according to ethnicity or employed analyzer. According to the analytical method and age, reported reference values for AST show clinically significant differences, similar to ALT. These observations prove clinical laboratories' interest in updating their reference values according to sex, body mass index, age (especially when providing testing to pediatric or elderly populations), and the analytical method employed. If possible, a standardized method should be used, including sample supplementation with pyridoxal phosphate, to ensure the comparability of results between laboratories.
L'aspartate aminotransférase (ASAT) et l'alanine aminotransférase (ALAT) sont des enzymes intracellulaires impliquées dans le métabolisme des acides aminés. La mesure de leurs activités fait partie des examens biochimiques les plus couramment réalisés en pratique clinique, en particulier pour le dépistage, le diagnostic et le suivi des pathologies hépatiques. Les valeurs de référence de l'ALAT et de l'ASAT varient en fonction des caractéristiques individuelles et de la méthode d'analyse. Dans cet article, nous proposons une brève revue de ces sources de variations pour répondre à la question suivante : faut-il réexaminer et adapter les valeurs usuelles des transaminases ? Les valeurs usuelles rapportées pour l'ALAT montrent des différences cliniquement significatives selon la méthode analytique (plus élevées lors de l'emploi de phosphate pyridoxal), le sexe (plus élevées chez l'homme que chez la femme), l'indice de masse corporelle (corrélation positive) et l'âge (plus élevées chez les nourrissons et les personnes âgées). Ces études ne montrent pas de différences en fonction de l'origine ethnique ou de l'analyseur employé. Concernant l'ASAT, les valeurs usuelles rapportées montrent des différences cliniquement significatives selon la méthode analytique et l'âge, similaires à celles observées pour l'ALAT. Une méthode standardisée doit être utilisée de préférence, intégrant notamment l'emploi de phosphate de pyridoxal, pour assurer la comparabilité des résultats entre les laboratoires. Ces observations prouvent la nécessité pour les laboratoires cliniques d'actualiser leurs valeurs usuelles en fonction du sexe, de l'indice de masse corporelle, de l'âge (notamment pour les âges extrêmes : populations pédiatriques ou âgées) et de la méthode analytique employée.
Assuntos
Fígado , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Biomarcadores , Criança , Feminino , Humanos , Fígado/metabolismo , Masculino , Valores de ReferênciaRESUMO
INTRODUCTION: Ferritin is the major iron-storage glycoprotein found in all tissues. Ferritin glycosylation can be assessed by the differential affinities of ferritin glycoforms for Concanavalin A (ConA), a lectin. The fraction of serum ferritin bound to ConA is called "glycosylated ferritin" (GF). Low GF reflects macrophagic activation and is an essential biomarker used in adult-onset Still's disease (AOSD), macrophage activation syndrome (MAS) and Gaucher disease diagnosis and therapeutic management. To date, no complete assay description and method validation according to the ISO 15189 standard has been published. This study aimed to describe and validate our method used for GF measurement and describe GF values observed in patients. MATERIALS AND METHODS: Ferritin glycoforms were separated based on their affinities for ConA using commercially available TRIS-barbital buffer, Sepharose and ConA/Sepharose 4B gels. Ferritin concentrations were measured on the Siemens Dimension Vista 1500®. We analysed 16,843 GF values obtained between 2000 and 2021 from our database of patients. RESULTS: Optimal separation of ferritin glycoforms was obtained by 15-min incubation of serum with ConA/Sepharose at pH 8. The optimized volume were 0.4 mL for total serum ferritin (TSF) 30-1000 µg/L and 0.5 mL for TSF 1000-2500 µg/L. Serum with higher TSF should be pre-diluted in the TRIS-barbital buffer. Reproducibility of ferritin measurement in the TRIS-barbital buffer matrix was excellent (intra-assay CV < 1%; inter-assay CV < 4%). Reproducibility of GF assay was good (intra-assay CV < 10% for low and high ferritin samples, respectively; and inter-assay CV < 10%). Inter-operator variability was 21.6% for GF < 20%. Ferritin was stable for up to 3 days in the TRIS-barbital buffer. An inter-laboratory exchange program conducted with another French hospital showed good agreement between results. In our database, <20% GF levels were scarce, compatible with the low prevalence of Still's disease, MAS, and Gaucher disease. The 95% confidence interval for GF was [26-58]%, lower than values described in the literature for healthy individuals. CONCLUSION: Thanks to good performances, this technique can become readily available for laboratories servicing patients with AOSD, MAS (including severe COVID-19 patients) and Gaucher disease patients.
Assuntos
Técnicas de Química Analítica/métodos , Concanavalina A/metabolismo , Ferritinas/sangue , Síndrome de Ativação Macrofágica/sangue , Doença de Still de Início Tardio/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Ferritinas/metabolismo , Doença de Gaucher/sangue , Doença de Gaucher/metabolismo , Humanos , Síndrome de Ativação Macrofágica/metabolismo , Ligação Proteica , Doença de Still de Início Tardio/metabolismoRESUMO
BACKGROUND: Since the COVID-19 pandemic began, a cohort of Multisystem inflammatory syndrome in children (MIS-C) patients has been described. Cardiac involvement is found in 80-85% patients, typically with cardiac dysfunction with or without cardiogenic shock. Here, three cardiac biomarkers, BNP, NT-proBNP and Galectin-3 were compared for the first time in MIS-C in a unique cohort of hospitalized French children. METHODS: Fourteen children with MIS-C hospitalized at Necker-Enfants Malades for cardiac management during the first three COVID-19 waves (March 2020-March 2021) were included. All had positive SARS-CoV-2 serology and proven cardiac involvement assessed by transthoracic echocardiography. NT-proBNP, BNP and Galectin-3 were measured at admission, discharge and first follow-up clinic. RESULTS: All admission Galectin-3 measurements were comprised within the reference interval, both in patients with and without cardiogenic shock, and did not vary between admission, discharge and first follow-up clinic. Both median admission BNP and NT-proBNP were higher in children with cardiogenic shock than without. Median admission NT-proBNP was higher than its predictive positive value in heart failure in both groups of children, while median BNP was below its negative predictive value in children without cardiogenic shock but with cardiac dysfunction. CONCLUSIONS: Galectin-3 does not seem affected by MIS-C. NT-proBNP seems to increase more precociously than BNP possibly making it a more sensitive marker for screening of heart failure in MIS-C.
Assuntos
COVID-19 , Insuficiência Cardíaca , Biomarcadores , COVID-19/complicações , Criança , Galectina 3 , Humanos , Peptídeo Natriurético Encefálico , Pandemias , Fragmentos de Peptídeos , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
SLC37A4-CDG is an emerging congenital disorder of glycosylation which is characterized by a dominant inheritance and a major coagulopathy originating from the liver. Recent studies took interest in the biochemical alterations found in this CDG and showed that they consisted of multiple glycosylation abnormalities, which result from mislocalization of the endoplasmic reticulum glucose-6-phosphate transporter and associated Golgi homeostasis defects. In this work, we highlight in six affected individuals abnormal patterns for various serum N-glycoproteins and bikunin proteoglycan isoforms, together with specific alterations of the mass spectra of endoglycosidase H-released serum N-glycans. Collectively, these data complement previous findings, help to better delineate SLC37A4-CDG and could present interest in diagnosing this disease.
Assuntos
Defeitos Congênitos da Glicosilação , Antiporters/metabolismo , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/metabolismo , Retículo Endoplasmático/metabolismo , Glicosilação , Complexo de Golgi , Humanos , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , PolissacarídeosRESUMO
Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.
Assuntos
Biomarcadores/metabolismo , COVID-19/complicações , Endocardite/diagnóstico , Miocárdio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , COVID-19/diagnóstico , COVID-19/epidemiologia , Endocardite/epidemiologia , Endocardite/virologia , Feminino , França/epidemiologia , Coração/virologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/virologia , Pandemias , Valor Preditivo dos Testes , Prognóstico , SARS-CoV-2/fisiologiaRESUMO
We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Targeted gene sequencing in P1 revealed pathogenic ATP6V0A2 variants, shared by her affected older brother. In P2 and P3, whole exome sequencing revealed a homozygous COG4 variant of unknown significance. In all affected individuals, transferrin analysis was normal. Mass-spectrometry based serum N-glycome analysis and two-dimensional electrophoresis (2-DE) of haptoglobin and of mucin core 1 O-glycosylated apolipoprotein C-III (apoC-III) were performed. All results of second-line N-glycosylation analyses were initially normal. However, apoC-III 2-DE revealed characteristic "apoC-III1" pattern in P1 and specific "apoC-III0" patterns in P2 and P3. In P2 and P3, this allowed reclassifying the variant as likely pathogenic according to ACMG guidelines. These cases highlight the existence of normal transferrin patterns in CDG with Golgi homeostasis disruption, putting the clinicians at risk of misdiagnosing patients. Furthermore, they show the potential of apoC-III 2-DE in diagnosing this type of CDG, with highly specific patterns in COG-CDG.