RÉSUMÉ
BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid ß-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists. PATIENTS AND METHODS: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022. RESULTS: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid ß-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity. CONCLUSIONS: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease.
Sujet(s)
Anémie , Maladie de Gaucher , Gammapathie monoclonale de signification indéterminée , Paraprotéinémies , Humains , Sujet âgé , Gammapathie monoclonale de signification indéterminée/complications , Gammapathie monoclonale de signification indéterminée/diagnostic , Gammapathie monoclonale de signification indéterminée/épidémiologie , Maladie de Gaucher/complications , Maladie de Gaucher/diagnostic , Maladie de Gaucher/épidémiologie , PrévalenceRÉSUMÉ
BACKGROUND: Gaucher disease (GD) is a rare, inherited, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid ß-glucosidase. Its diagnosis is achieved via measurements of acid ß-glucosidase activity in either fresh peripheral blood leukocytes or dried blood spots, and confirmed by identifying characteristic mutations in the GBA1 gene. Currently, several biomarkers are available for disease monitoring. Chitotriosidase has been used over the last 20 years to assess the severity of GD, but lacks specificity in GD patients. Conversely, the deacylated form of glucosylceramide, glucosylsphingosine (also known as lyso-Gb1), represents a more reliable biomarker characterized by its high sensitivity and specificity in GD. MAIN TEXT: Herein, we review the current literature on lyso-Gb1 and describe evidence supporting its usefulness as a biomarker for diagnosing and evaluating disease severity in GD and monitoring treatment efficacy. CONCLUSION: Lyso-Gb1 is the most promising biomarker of GD, as demonstrated by its reliability in reflecting disease burden and monitoring treatment response. Furthermore, lyso-Gb1 may play an important role in the onset of monoclonal gammopathy of uncertain significance, multiple myeloma, and Parkinson's disease in GD patients.
Sujet(s)
Maladie de Gaucher , Humains , Maladie de Gaucher/diagnostic , Maladie de Gaucher/génétique , Glucosylceramidase/génétique , Reproductibilité des résultats , Marqueurs biologiquesRÉSUMÉ
Acquired hemophilia A (AHA) is a rare coagulopathy characterized by hemorrhagic manifestations. It has been linked to various conditions, including autoimmune disorders, drugs, tumors, lymphoproliferative disorders, and infections. We present a case of AHA in a 71-year-old male patient with cutaneous hematoma occurring 8 days after vaccination for COVID-19. This report aims to highlight the risk of FVIII inhibitor development following an immune stimulus, thus improving our knowledge regarding possible vaccination-related adverse events. Furthermore, we underline how the potential risk of not recognizing disease manifestations promptly, together with specific coagulation alterations, could significantly affect the patient's outcome. Adequate management plans and the diffusion of shared guidelines are of fundamental importance in order to prevent the development of life-threatening complications and initiate appropriate treatment as soon as possible. DATA AVAILABILITY: All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.
Sujet(s)
COVID-19 , Hémophilie A , Mâle , Humains , Sujet âgé , Hémophilie A/complications , Hémophilie A/diagnostic , Hémophilie A/traitement médicamenteux , Vaccins contre la COVID-19/effets indésirables , COVID-19/diagnostic , COVID-19/prévention et contrôle , COVID-19/complications , Hémorragie/complicationsRÉSUMÉ
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease. Vaccination has been reported to be a trigger of onset and relapse of autoimmune diseases. We evaluated after mRNA COVID-19 vaccination 32 adult patients previously diagnosed with iTTP by means of weekly monitoring of complete blood count and ADAMTS13 testing. Thirty of 32 patients received at least one dose of Pfizer-BioNTech, the remaining two received Moderna. A total of five patients, all vaccinated with Pfizer-BioNTech, had a biochemical relapse at a median post-vaccination time of 15 days following the second or third vaccine dose, presenting without measurable ADAMTS13 activity and a median anti- ADAMTS13 autoantibody value of 34 U/mL. Four of five cases had concomitant clinical relapse and were treated with corticosteroids alone or daily sessions of plasma exchange and caplacizumab, while one patient was closely monitored with ADAMTS13 with no onset of anemia and thrombocytopenia. Although the benefits of vaccination exceed its potential risks, clinicians should be aware that iTTP relapse might follow COVID-19 vaccination. Therefore, laboratory and clinical monitoring of iTTP patients should be done in the first post-vaccination month, in order to promptly diagnose and treat any relapse.