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1.
Blood ; 137(4): 493-499, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-32905580

RESUMO

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.


Assuntos
Agamaglobulinemia/genética , Linfócitos B/patologia , Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Síndromes de Imunodeficiência/genética , Linfopenia/genética , Adulto , Animais , Linfócitos B/metabolismo , Criança , Pré-Escolar , Cromossomos Humanos Par 5/genética , Códon sem Sentido , Consanguinidade , Doença de Crohn/genética , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Cardiopatias Congênitas/genética , Humanos , Infecções/etiologia , Mutação com Perda de Função , Masculino , Camundongos , Neutropenia/genética , Linhagem , Dissomia Uniparental , Sequenciamento do Exoma
5.
J Allergy Clin Immunol Glob ; 2(1): 76-78, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37780104

RESUMO

Background: Hereditary angioedema (HAE) is a genetic condition characterized by dysregulation of the contact (kallikrein-bradykinin) pathway, leading to recurrent episodes of angioedema. Objective: This project sought to determine whether a suspicion index screening tool using electronic health record (EHR) data can identify patients with an increased likelihood of a diagnosis of HAE. Methods: A suspicion index screening tool for HAE was created and validated by using known patients with HAE from the medical literature as well as positive and negative controls from HAE-focused centers. Through the use of key features of medical and family history, a series of logistic regression models for 5 known genetic causes of HAE were created. Top variables populated the digital suspicion scoring system and were run against deidentified EHR data. Patients at 2 diverse sites were categorized as being at increased, possible, or no increased risk of HAE. Results: Prediction scoring using the strongest 13 variables on the "real-world" EHR-positive control data identified all but 1 patient with C1 inhibitor deficiency and patient with non-C1 inhibitor deficiency without false-positive results. The 2 missed patients had no documented family history of HAE in their EHR. When the prediction scoring variables were expanded to 25, the screening algorithm approached 100% sensitivity and specificity. The 25-variable algorithm run on general population EHR data identified 26 patients at the medical centers as being at increased risk for HAE. Conclusions: These results suggest that development, validation, and implementation of suspicion index screening tools can be useful to aid providers in identifying patients with rare genetic conditions.

6.
Pediatr Dermatol ; 29(2): 224-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22409475

RESUMO

Wells' syndrome is a rare disease that is even more uncommon in childhood. This case report illustrates the potential devastating extent of the disease and highlights the unusual presentation of bullae in a child. It is imperative to consider Wells' syndrome in patients with presumed cellulitis and eosinophilia who fail to respond to antibiotics.


Assuntos
Celulite (Flegmão)/diagnóstico , Eosinofilia/diagnóstico , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Biópsia , Vesícula/diagnóstico , Unidades de Queimados , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/patologia , Criança , Eosinofilia/tratamento farmacológico , Eosinofilia/patologia , Humanos , Masculino , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
J Allergy Clin Immunol Pract ; 8(6): 1866-1874, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32298850

RESUMO

Chronic urticaria (CU) and angioedema can occur at any age. Although most CU with or without angioedema occurs in adults, it can also present in children or the elderly and can complicate pregnancy and breast-feeding. The presentations of CU and angioedema are different in children, middle-aged adults, and older patients as are the differential diagnoses. Therefore, the management of CU and angioedema in these different age groups and special populations needs to take into account the age-specific features of urticaria and angioedema. Here, we describe the evaluation, diagnosis, and treatment of CU and angioedema in children, middle-aged adults, and older patients. This review focuses on CU with or without angioedema and does not discuss acute urticaria or bradykinin-mediated angioedema.


Assuntos
Angioedema , Urticária Crônica , Urticária , Adulto , Idoso , Angioedema/diagnóstico , Angioedema/epidemiologia , Angioedema/terapia , Bradicinina , Criança , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Urticária/diagnóstico , Urticária/tratamento farmacológico
10.
J Allergy Clin Immunol Pract ; 6(1): 227-235, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28803180

RESUMO

BACKGROUND: The factors associated with poor asthma control, exacerbations, and health care utilization in black adolescents are complex and not well understood. Although psychological comorbidities such as anxiety are common in patients with asthma, these have not been studied in this population. OBJECTIVE: This study characterized anxiety and associated asthma features in a cohort of black inner-city adolescents with persistent asthma and determined the association between anxiety symptoms, persistent uncontrolled asthma, and prospective health care utilization over 1 year. METHODS: Eighty-six black adolescents were enrolled, phenotyped, and screened for anxiety symptoms with the Hospital Anxiety and Depression Scale anxiety subscale (HADS-A). Participants were telephoned every 2 months and a second study visit was completed at 1 year. Primary outcomes included persistent uncontrolled asthma, asthma exacerbations requiring systemic corticosteroids, and unscheduled health care utilization during the 1-year study period. RESULTS: A total of 31% (n = 27) of adolescents had probable anxiety (ie, HADS-A score >7) and 27% (n = 23) had possible anxiety (ie, HADS-A score 5-7) at the baseline visit. Anxiety symptoms were associated with poorer asthma control, more impaired quality of life, and more insomnia symptoms. Adolescents with probable anxiety disorders also had increased odds of persistent uncontrolled asthma and emergency department utilization, with no differences in physician visits or systemic corticosteroid receipt. CONCLUSIONS: Inner-city black adolescents with persistent asthma have a high prevalence of anxiety symptoms associated with poorer asthma control, impaired quality of life, insomnia, and increased prospective emergency department utilization for asthma. Routine screening for anxiety disorders may be useful in the clinical management of adolescents with asthma.


Assuntos
Ansiedade/epidemiologia , Asma/epidemiologia , Negro ou Afro-Americano , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Urbana , Adolescente , Adulto , Ansiedade/diagnóstico , Asma/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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