RESUMO
PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome caused by mutations in PSTPIP1 is a rare inflammatory disorder that can be easily misdiagnosed. It is characterized by anemia, arthritis, cutaneous inflammation, recurrent infections, growth failure, hepatosplenomegaly, lymphadenopathy, hyperzincemia/hypercalprotectinemia, neutropenia, thrombocytopenia, and elevated inflammatory indicators. This study describes the cases of two pediatric female patients with long-standing recurrent arthralgia in different parts of the extremities and severe anemia, respectively, who were misdiagnosed and treated for aseptic necrosis of the femoral head and severe autoimmune hemolytic anemia, respectively. High-throughput sequencing analysis revealed a de novo heterozygous missense mutation (c.748G > A, p. Glu250Lys) in exon 11 of PSTPIP1 (NM_003978.5) in both patients, which supported a diagnosis of PAMI. The patients were treated with prednisone and etanercept, which improved their symptoms, but neutropenia remained unchanged. These cases highlight the importance of genetic assessment for the accurate diagnosis of PAMI and to ensure adequate and timely treatment of these patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Anemia/diagnóstico , Proteínas do Citoesqueleto/genética , Inflamação/diagnóstico , Neutropenia/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Anemia/complicações , Anemia/genética , Anemia/patologia , Artrite/complicações , Artrite/diagnóstico , Artrite/genética , Artrite/patologia , Criança , Pré-Escolar , Proteínas do Citoesqueleto/deficiência , Erros de Diagnóstico/prevenção & controle , Feminino , Heterozigoto , Humanos , Inflamação/complicações , Inflamação/genética , Inflamação/patologia , Erros Inatos do Metabolismo dos Metais , Mutação/genética , Células Mieloides/patologia , Neutropenia/complicações , Neutropenia/genética , Neutropenia/patologia , FenótipoRESUMO
OBJECTIVE: To investigate the presence of Cosmc gene mutation in children with Henoch-Schönlein purpura (HSP) and the association between Cosmc gene mutation and the susceptibility to HSP. MESULTS: Eighty-four children who were diagnosed with HSP between March 2014 and December 2015 were selected as the HSP group. Fifty-eight healthy volunteers matched for age and sex were enrolled as the control group. Fasting venous blood (5â mL) from the two groups was collected in EDTA anticoagulated tubes, followed by the isolation of peripheral blood mononuclear cells (PBMCs) through density gradient centrifugation. Genomic DNA was extracted from PBMCs according to the manufacturer's protocol, and the whole exon region of Cosmc gene was amplified by touch-down polymerase chain reaction (touch-down PCR). The PCR products were identified by 1% agarose gel and sequenced in order to further examine the association between Cosmc gene mutation and the susceptibility to HSP. RESULTS: Sequencing results showed two mutations (c.393T>A and c.72A>G) of Cosmc gene in children with HSP. There were no significant differences in the genotype and allele frequencies at the two loci between the HSP and control groups, and this distribution was not associated with sex. CONCLUSIONS: The mutations c.393T>A and c.72A>G in the exon region of Cosmc gene in children with HSP are not associated with the onset of HSP.
Assuntos
Predisposição Genética para Doença , Vasculite por IgA/genética , Chaperonas Moleculares/genética , Mutação , Criança , Pré-Escolar , Feminino , Humanos , Vasculite por IgA/etiologia , MasculinoRESUMO
BACKGROUND: Treatment of systemic-onset juvenile idiopathic arthritis (So-JIA) is challenging, and the efficacy of injectable recombinant human tumor necrosis factor type 1 receptor-antibody fusion protein (etanercept) on So-JIA has been controversial. METHODS: We retrospectively studied 12 patients with refractory systemic juvenile arthritis treated with etanercept at our hospital in the past 5 years. The 12 patients were divided into a corticosteroid-dependent group (n=7) and an ineffective group (n=5) on the basis of their responses to treatment before the administration of etanercept. Etanercept was added to the treatment without substantially changing the original regimens in general, and doses, and signs of efficacy including alleviation or resolution of symptoms such as high fever, inflammatory arthropathy, eruption rash, hydrohymenitis, as well as changes in the levels of laboratory inflammatory markers such as the white blood cell count, erythrocyte sedimentation rate, levels of C-reactive protein and serum ferritin were recorded. RESULTS: Etanercept was withdrawn after the first dose from one patient in the corticosteroid-dependent group because of a systemic allergic rash, and was also withdrawn from one patient in the ineffective group after 2 months of treatment owing to inefficacy; the remaining 10 patients completed the entire treatment protocol, at which point etanercept was discontinued. At that time, clinical symptoms and laboratory inflammatory markers of the remaining patients were within the normal range and the mean dose of prednisone was 0.18 mg/kg per day, an 81% decrease from the mean dose at baseline. At present, the corticosteroid has been discontinued and only methotrexate maintenance treatment is used in 3 patients; the other 7 patients are treated with prednisone and methotrexate maintenance therapy. All of the 10 patients are in a medicated remission with no recurrence. CONCLUSIONS: In the treatment of patients with refractory So-JIA, the principles of individual therapy and combinations of drugs should be followed. Etanercept is an important and valid candidate for use in such combined treatment strategies.