RESUMO
OBJECTIVES: To examine the phenotypes and perform next-generation sequencing in children with early-onset protein-losing enteropathy. STUDY DESIGN: We performed a retrospective review of 27 children with early-onset protein-losing enteropathy. Patients were characterized on clinical, immunologic, and systemic involvements. Targeted gene panel sequencing and whole-exome sequencing were performed in 9 patients. RESULTS: In 27 patients (55.6% male), median age of disease onset was 173 days, and 59.3% had onset of disease before 1 year of age. Initial gastrointestinal symptoms included diarrhea (74.1%), vomiting (33.3%), and abdominal distention (48.1%). All patients had hypoalbuminemia, with an average serum albumin concentration of 20.2 ± 5.4 g/L. Hypogammaglobulinemia was identified in 72% of the patients. Upper endoscopy showed typical presentation of intestinal lymphangiectasia (n = 13). Patients frequently received intravenous albumin and immunoglobulin infusions as well as parenteral nutrition. Next-generation sequencing in 9 patients with available DNA showed 1 patient had compound heterozygous CCBE1 mutations and 2 had novel homozygous DGAT1 mutations. Monogenic diseases were identified in 3 of 9 patients who underwent genetic sequencing. Three subjects (11.1%) died, of whom 2 had homozygous DGAT1 mutations. No significant correlation was found between age of symptom onset, serum albumin, serum IgG, lymphocyte count, CD4+ cells, and mortality. CONCLUSIONS: Monogenic diseases may be observed in children with early-onset protein-losing enteropathy, and genetic evaluation with next-generation sequencing should be considered.
Assuntos
Povo Asiático/genética , Proteínas de Ligação ao Cálcio/genética , Diacilglicerol O-Aciltransferase/genética , Mutação/genética , Enteropatias Perdedoras de Proteínas/etnologia , Enteropatias Perdedoras de Proteínas/genética , Proteínas Supressoras de Tumor/genética , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Fenótipo , Enteropatias Perdedoras de Proteínas/diagnóstico , Estudos RetrospectivosRESUMO
Protein-losing gastroenteropathy (PLGE) is a rare manifestation of primary Sjögren's syndrome (SS). We report a case of a 41-year-old Japanese man, who is the first male patient, with PLGE associated with primary SS. Although serum anti-SSA and SSB antibodies were detected, he had no subjective sicca symptoms. He had multiple annular erythema: a characteristic skin manifestation of Asian SS patients. A diagnosis of PLGE was made from results of (99m)Tc-labelled albumin scintigraphy and a faecal alpha-1-antitrypsin clearance test. Intravenous administration of high-dose glucocorticoid was not effective, but pulse methylprednisolone therapy alleviated disease manifestations. As all cases of PLGE associated with primary SS have been reported from East Asia, this complication could be essentially limited to Asian patients.