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Introduction: X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disorder characterized by recurrent infections, severe hypogammaglobulinemia, and a deficiency of circulating B cells. While the hallmark clinical manifestations of XLA typically include the respiratory, dermatological, and gastrointestinal systems, renal involvement is infrequent. In this article, we report two cases of XLA with concurrent renal disease, supplemented with a review of documented cases. Case description: The two cases described involve twin brothers, both presenting with respiratory tract infections and renal manifestations. Subsequent genetic testing confirmed the diagnosis of XLA. The younger brother exhibited improvement following intravenous immunoglobulin (IVIG) therapy and anti-infection treatment. Due to financial constraints, the older brother received only anti-infection and symptomatic treatments. Seven months after discharge, the older brother developed nephritis. However, he showed improvement following IVIG treatment. Conclusion: Immune profiling and genetic testing should be considered in male children with recurrent infections to facilitate the effective diagnosis of XLA. Regular monitoring is also imperative to detect and treat immune-mediated renal diseases in patients with XLA.
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Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Inmunoglobulinas Intravenosas , Humanos , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Agammaglobulinemia/complicaciones , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Niño , PreescolarRESUMEN
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare disease first reported in 2020, most commonly seen in men aged 56-75 years old. Common clinical features include skin lesions (83.5%), fever (63.6%), relapsing chondritis (36.4%), venous thrombosis (34.7%) and lymph node enlargement (33.9%). The patient is a man in his 40s who presented with testicular and lower extremity pain, followed by a rash and bicytopenia. He was initiated on corticosteroids and sulfasalazine. He was found to have mediastinal lymphadenopathy and underwent an endobronchial ultrasound and transbronchial needle aspiration followed by a video-assisted thoracic surgery biopsy which were unrevealing. Eventually, an ubiquitin-like modifier activating enzyme (UBA-1) gene analysis was performed that was consistent with VEXAS syndrome. Patients with VEXAS syndrome usually present with a red or violaceous rash and dyspnoea. Laboratory abnormalities include anaemia, elevated mean corpuscular volume, thrombocytopenia and elevated inflammatory markers. Diagnosis is based on the genetic mutation and associated symptoms. The treatment includes steroids and Janus kinase (JAK) inhibitors, specifically ruxolitinib.
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Linfadenopatía , Humanos , Masculino , Linfadenopatía/etiología , Adulto , Enzimas Activadoras de Ubiquitina/genética , Enfermedades del Mediastino/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Diagnóstico Diferencial , Síndrome , Nitrilos , Pirazoles , PirimidinasRESUMEN
PURPOSE: To define the clinical and histological characteristics of nephritis in patients with X-linked agammaglobulinemia (XLA) and their immunological profiles. METHODS: The clinical, immunological, and histological findings of nine patients with XLA and nephritis were retrospectively analyzed. RESULTS: Based on kidney histological findings, patients with XLA and nephritis could be divided into two groups, viz., chronic glomerulonephritis (CGN) and tubulointerstitial nephritis (TIN). The two groups showed different immunological profiles. Patients in the CGN group exhibited an atypical immunological profile of XLA, with pathogenic leaky B cells producing immunoglobulins that may play a role in forming immune complexes and causing immune-mediated glomerulonephritis. In contrast, patients in the TIN group exhibited a typical immunological profile of XLA, suggesting that antibody-independent/other BTK-dependent mechanisms, or immunoglobulin replacement therapy (IgRT)-related immune/nonimmune-mediated nephrotoxicity causes TIN. CONCLUSION: Nephritis occurring in patients with XLA could have links between their renal pathology and immunological status. Careful observation is recommended to detect kidney pathology in patients with XLA on IgRT.
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Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Fenotipo , Humanos , Agammaglobulinemia/inmunología , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Masculino , Adolescente , Niño , Adulto , Estudios Retrospectivos , Preescolar , Adulto Joven , Agammaglobulinemia Tirosina Quinasa/genética , Nefritis Intersticial/inmunología , Nefritis Intersticial/diagnóstico , Riñón/patología , Riñón/inmunología , Linfocitos B/inmunología , Femenino , Glomerulonefritis/inmunología , Glomerulonefritis/diagnóstico , Nefritis/inmunología , Nefritis/diagnóstico , Nefritis/etiologíaRESUMEN
Protoporphyria is a subtype of porphyria characterized primarily by painful phototoxic skin reactions after light exposure at specific wavelengths. Historically, phototherapy is not contraindicated in patients with protoporphyria since there have not been any reports of phototoxic reactions. However, patients with protoporphyria are advised to avoid direct sunlight. In this case report, we describe a neonate not known to have X-linked protoporphyria who received phototherapy for 1 to 2 hours. Within hours after initiation of phototherapy, this neonate developed a life-threatening reaction consisting of rash over the distribution of phototherapy, acute liver failure with coagulopathy, diffuse hypotonia with diaphragmatic failure, and subsequent acute respiratory failure that required mechanical ventilation. As in this case, patients with protoporphyria-related acute liver failure can have signs and symptoms similar to that of an acute hepatic porphyria attack. Neither neonatal reactions to phototherapy nor liver failure temporally associated with phototherapy have been reported in patients with X-linked protoporphyria. Early recognition of this entity is crucial in light of potential life-threatening complications. Therefore, providers must react quickly when neonates have abnormal reactions to phototherapy and consider protoporphyria in the differential diagnosis.
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Fototerapia , Humanos , Recién Nacido , Fototerapia/efectos adversos , Fototerapia/métodos , Masculino , Protoporfiria Eritropoyética/terapia , Protoporfiria Eritropoyética/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/diagnósticoRESUMEN
This case report presents the diagnostic journey of a man in his mid-70s who experienced shortness of breath, cough, recurrent episodes of fever, weight loss, pruritic erythroderma, uveitis and macrocytic anaemia. The initial diagnosis of cryptogenic organising pneumonia was made based on antibiotic refractory infiltrates seen in the lung CT scan. The patient initially responded favourably to immunosuppression but experienced a recurrence of symptoms when the corticosteroid dose was tapered. Despite ongoing systemic inflammation and refractory symptoms, it took nearly a year to establish the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic) syndrome. This case highlights the challenges in diagnosing and managing VEXAS syndrome due to its recent discovery and limited awareness in the medical community, as well as the need to consider this syndrome as a rare differential diagnosis of therapy-refractory pulmonary infiltrates.
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Tomografía Computarizada por Rayos X , Humanos , Masculino , Diagnóstico Diferencial , Anciano , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Tos/etiología , Disnea/etiología , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Fiebre/etiología , Pulmón/diagnóstico por imagen , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Síndrome , Dermatitis Exfoliativa/diagnóstico , Dermatitis Exfoliativa/etiología , Neumonía en Organización Criptogénica/diagnóstico , Neumonía en Organización Criptogénica/tratamiento farmacológicoRESUMEN
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.
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Hemorragia , Enfermedades Pulmonares Intersticiales , Alveolos Pulmonares , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico , Alveolos Pulmonares/patología , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Pulmonares/patología , Vacuolas/patología , Persona de Mediana Edad , Síndrome , Enzimas Activadoras de UbiquitinaRESUMEN
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which cause dysregulation of ubiquitin-mediated processes. This case describes a 71-year-old male patient with VEXAS syndrome who presented with refractory lung inflammation with a pattern similar to computed tomography hypersensitivity pneumonitis, a novel finding in VEXAS syndrome. The presented clinical case highlights the protean involvement of the lung in VEXAS syndrome and emphasizes the importance of considering interstitial lung disease in the differential diagnosis.
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Alveolitis Alérgica Extrínseca , Enzimas Activadoras de Ubiquitina , Humanos , Masculino , Anciano , Alveolitis Alérgica Extrínseca/genética , Alveolitis Alérgica Extrínseca/diagnóstico , Enzimas Activadoras de Ubiquitina/genética , Síndrome , Vacuolas , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Mutación , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Pulmón/patologíaAsunto(s)
Anticuerpos Monoclonales Humanizados , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades del Sistema Inmune/congénitoRESUMEN
X-linked dystonia parkinsonism (XDP) is a neurogenetic combined movement disorder involving both parkinsonism and dystonia. Complex, overlapping phenotypes result in difficulties in clinical rating scale assessment. We performed wearable sensor-based analyses in XDP participants to quantitatively characterize disease phenomenology as a potential clinical trial endpoint. Wearable sensor data was collected from 10 symptomatic XDP patients and 3 healthy controls during a standardized examination. Disease severity was assessed with the Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS) and Burke-Fahn-Marsden dystonia scale (BFM). We collected sensor data during the performance of specific MDS-UPDRS/BFM upper- and lower-limb motor tasks, and derived data features suitable to estimate clinical scores using machine learning (ML). XDP patients were at varying stages of disease and clinical severity. ML-based algorithms estimated MDS-UPDRS scores (parkinsonism) and dystonia-specific data features with a high degree of accuracy. Gait spatio-temporal parameters had high discriminatory power in differentiating XDP patients with different MDS-UPDRS scores from controls, XDP freezing of gait, and dystonic/non-dystonic gait. These analyses suggest the feasibility of using wearable sensor data for deriving reliable clinical score estimates associated with both parkinsonian and dystonic features in a complex, combined movement disorder and the utility of motion sensors in quantifying clinical examination.
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Trastornos Distónicos , Enfermedades Genéticas Ligadas al Cromosoma X , Aprendizaje Automático , Dispositivos Electrónicos Vestibles , Humanos , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/fisiopatología , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Masculino , Adulto , Persona de Mediana Edad , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/diagnóstico , Índice de Severidad de la Enfermedad , Femenino , MarchaAsunto(s)
Absceso , Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Masculino , Absceso/diagnóstico , Absceso/complicaciones , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/complicaciones , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVE: The two commonly used diagnostic methods for taurodontism are susceptible to aging changes, mastication wear and other factors. Therefore, this study proposed an improved diagnostic method for taurodontism, and compared it with the previous two methods as a supplement for taurodontism diagnosis. METHODS: The included patients were aged 10-89 years and admitted to the Department of Stomatology of Hebei Eye Hospital from June 1, 2022 to May 31, 2023. Eighty cone-beam computed tomography images were divided equally into 4 groups: 10-29, 30-49, 50-69, and 70-89 years old. The right mandibular first molars were selected as measurement objects. Firstly, |BD| and taurodontism index (TI)-related parameters were measured using Shifman and Chanannel's method and crown-body(CB) and root (R) lengths was measured by Seow and Lai's method. The improved method used the length from the cementoenamel junction(CEJ) to the root bifurcation point(body, B)and the root length(root, R)as the measurement objects. Finally, TI, CB/R ratios, and B/R ratios were calculated according to the formulas given below. One-way ANOVA analysis was mainly used to compare the differences in the values, indices and ratios of taurodontism among different age groups (p<0.05). RESULTS: With the increase of age, |BD| and TI values decreased significantly (p<0.01). The CB/R ratios of 70-89 years group were significantly lower than those of the other three groups (p<0.01). Ratios derived from the improved method were significantly lower in the 70-89 years than in 10-29 years group (p<0.05). CONCLUSIONS: The |BD| and TI parameters proposed by Shifman and channel are significantly influenced by age. The measurements of Seow and Lai (CB/R ratios) were less affected by age compared with those of the former. The improved method(B/R ratios) was least affected by age, which would reduce error and bias in the measurement of taurodontism and obtain more objective results in older patients.
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Tomografía Computarizada de Haz Cónico , Cavidad Pulpar/anomalías , Humanos , Anciano , Persona de Mediana Edad , Adolescente , Adulto , Anciano de 80 o más Años , Niño , Femenino , Masculino , Adulto Joven , Tomografía Computarizada de Haz Cónico/métodos , Diente Molar/diagnóstico por imagen , Anomalías Dentarias/diagnóstico por imagen , Anomalías Dentarias/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnósticoRESUMEN
OBJECTIVE: The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS: We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS: All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION: Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.
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Canales de Cloruro , Enfermedad de Dent , Monoéster Fosfórico Hidrolasas , Humanos , Masculino , Niño , Canales de Cloruro/genética , Estudios Retrospectivos , Preescolar , China/epidemiología , Enfermedad de Dent/genética , Enfermedad de Dent/diagnóstico , Monoéster Fosfórico Hidrolasas/genética , Mutación , Proteinuria/genética , Adolescente , Hipercalciuria/genética , Nefrocalcinosis/genética , Nefrolitiasis/genética , Lactante , Pruebas Genéticas , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Mutación Missense , Femenino , Glomeruloesclerosis Focal y Segmentaria/genética , Riñón/patología , Pueblos del Este de AsiaAsunto(s)
Arritmias Cardíacas , Gigantismo , Cardiopatías Congénitas , Discapacidad Intelectual , Neoplasias Pancreáticas , alfa-Fetoproteínas , Humanos , Neoplasias Pancreáticas/patología , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Cardiopatías Congénitas/patología , Discapacidad Intelectual/patología , Arritmias Cardíacas/etiología , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Masculino , Niño , FemeninoRESUMEN
BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.
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Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Glomerulonefritis por IGA , Humanos , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Masculino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Niño , Inmunoglobulinas Intravenosas/uso terapéutico , Glucocorticoides/uso terapéutico , Ácido Micofenólico/uso terapéutico , Inmunosupresores/uso terapéuticoAsunto(s)
Electrorretinografía , Enfermedades Hereditarias del Ojo , Enfermedades Genéticas Ligadas al Cromosoma X , Ceguera Nocturna , Humanos , Ceguera Nocturna/fisiopatología , Ceguera Nocturna/diagnóstico , Femenino , Electrorretinografía/métodos , Lactante , Enfermedades Hereditarias del Ojo/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Miopía/fisiopatología , Miopía/diagnóstico , Diagnóstico DiferencialAsunto(s)
Agammaglobulinemia , Citometría de Flujo , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Agammaglobulinemia/genética , Agammaglobulinemia/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Masculino , Niño , Preescolar , Adolescente , Estudios de Cohortes , Lactante , Fenotipo , Estudios de Asociación GenéticaRESUMEN
A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed a large-for-gestational-age foetus with a large abdominal circumference and liver, ventricular septal defect, right prominent renal pelvis and echogenic bowel. Antenatal genetic tests for overgrowth syndromes were negative. The mother had early onset pre-eclampsia. After birth, an overgrowth syndrome was still suspected despite the baby having normal birth parameters. Raw data of the trio whole exome sequencing from the amniocentesis sample were manually inspected. Hemizygous exon 7 deletion in the GPC3 gene was found, and a postnatal diagnosis of Simpson-Golabi-Behmel syndrome, a rare overgrowth syndrome, was made. This case report discusses the significance of antenatal findings, an atypical presentation of a rare syndrome and the obstacles of diagnostic genetic testing.
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Enfermedades Genéticas Ligadas al Cromosoma X , Gigantismo , Cardiopatías Congénitas , Discapacidad Intelectual , Femenino , Humanos , Recién Nacido , Embarazo , Arritmias Cardíacas , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Gigantismo/diagnóstico , Gigantismo/genética , Glipicanos/genética , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genéticaRESUMEN
VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men older than 50 years, caused by somatic mutation in the UBA1 gene, a X-linked gene involved in the activation of ubiquitin system. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) that are responsible for a significant morbidity and mortality. The therapeutic management is currently poorly codified but is based on two main approaches: controlling inflammatory symptoms (by using corticosteroids, JAK inhibitor or tocilizumab) or targeting the UBA1-mutated hematopoietic population (by using azacitidine or allogeneic hematopoietic stem cell transplantation). Supportive care is also important and includes red blood cell or platelet transfusions, erythropoiesis stimulating agents, thromboprophylaxis and anti-infectious prophylaxis. The aim of this review is to provide a current overview of the VEXAS syndrome, particularly focusing on its pathophysiological, diagnostic and therapeutic aspects.
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Mutación , Humanos , Masculino , Síndrome , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/terapia , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Persona de Mediana Edad , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enzimas Activadoras de UbiquitinaRESUMEN
OBJECTIVE: To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Three patients with IPEX syndrome diagnosed at the Children's Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored. RESULTS: All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c.1222G>A (p.V408M), c.767T>C (p.M256T) and c.1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. CONCLUSION: FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.