A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Long-term restoration of alpha-L-iduronidase activity in fibroblasts from patients with mucopolysaccharidosis type I after non-viral gene transfer

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of alpha-L-iduronidase (IDUA). Limitations such as the need for weekly injections, high morbidity and mortality, and high cost of current treatments show that new approaches to treat this disease are required. In this study, we aimed to correct fibroblasts from a patient with MPS I using non-viral gene therapy. Using a plasmid encoding the human IDUA cDNA, we achieved stable high IDUA levels in transfected fibroblasts up to 6 months of treatment. These results serve as proof of concept that a non-viral approach can correct the enzyme deficiency in cells of patients with lysosomal storage disorders, which can be used as a research tool for a series of disease aspects. Future studies should focus on showing if this approach can be useful in small animals and clinical trials (AU)

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome / Desfechos neurológicos após transplante de células tronco hematopoiéticas na adrenoleucodistrofia ligada ao X, forma cerebral, na leucodistrofia metacromática de início tardio e na síndrome de Hurler

ABSTRACT Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD). Objective To describe survival and neurological outcomes after HSCT for these disorders. Methods Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

RESUMO O transplante de células tronco hematopoiéticas (TCTH) é o único tratamento disponível para o envolvimento neurológico de doenças como a leucodistrofia metacromática (MLD), a mucopolissacaridose tipo I-Hurler (MPS-IH) e a adrenoleucodistrofia (CALD). Objetivos Descrever a sobrevida e os desfechos neurológicos após o TCTH nessas doenças. Métodos Sete pacientes CALD, 2 MLD e 2 MPS-IH realizaram TCTH entre 2007 e 2014. Avaliações neurológicas, ressonância nuclear magnética e estudos bioquímicos e moleculares foram feitos no baseline e repetidos quando apropriado. Resultados Desfechos favoráveis foram obtidos em 4/5 TCTH de doadores relacionados e em 3/6 não relacionados. Dois pacientes faleceram de complicações do procedimento. Nove transplantados sobreviveram após uma mediana de 3,7 anos: estabilização neurológica foi obtida em 5/6 CALD, ½ MLD e em um caso MPS-IH. As lesões encefálicas de um caso MPS-IH reduziram-se quatro anos após o TCTH. Conclusão Bons desfechos foram obtidos quando o TCTH foi feito antes da vida adulta, cedo no curso clínico e/ou a partir de um doador relacionado.

Enzyme Replacement Therapy With Elosulfase Alfa Decreases Storage of Glycosaminoglycan in White Blood Cells of Patients With Morquio A Syndrome

Abstract Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT) was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG) storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W) versus infusions every other week (ERT-EOW) versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.

Gorlin-Goltz syndrome: case report and review of literature

Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.

Septic shock inppatient with disseminated histoplasmosis associated with aids: a case report / Choque septico em paciente com histoplasmose disseminada associada a AIDS: relato de caso

SUMMARY Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, which may present itself as a serious infection in immunocompromised individuals. We present a case of 31-year-old female with newly diagnosed HIV infection and history of fever, general and respiratory symptoms and diffuse hyperchromic papules through the body. She was admitted, with rapid progression to septic shock, and the presence of neutrophils filled with yeast-like organisms was detected on peripheral blood smear hematoscopia on the third day of hospitalization. The following is a brief review on the clinical picture and management of histoplasmosis. .

RESUMO A histoplasmose é micose sistêmica causada por Histoplasma capsulatum, a qual pode se apresentar de forma grave em indivíduos imunocomprometidos. Neste trabalho, apresenta-se o caso de paciente feminino, 31 anos, com diagnóstico recente de infecção por HIV e quadro de febre, sintomas gerais e respiratórios e pápulas hipercrômicas difusas pelo corpo. Foi internada, apresentando progressão rápida para choque séptico, sendo detectada a presença de leveduras inclusas em neutrófilos à hematoscopia no terceiro dia de internação. Apresenta-se uma revisão breve sobre a apresentação e o manejo clínico da histoplasmose. .

Actinomycosis affecting the spinal cord: a case report / Actinomicose comprometendo a medula espinhal: um relato de caso

Actinomycosis is a rare, chronic, suppurative, granulomatous infection caused by a group of gram-positive anaerobic bacteria belonging to the natural flora of the oral cavity and gastrointestinal and urogenital tracts. It may involve several organs. This case study refers to pulmonary actinomycosis with chest wall involvement and cord compression in a 29-year-old male who presented with fever, cough, hemoptysis, neck pain, and paresis and plegia of the lower limbs of 5-month duration.

A actinomicose é uma infecção rara, crônica, supurativa e granulomatosa, causada por um grupo de bactérias anaeróbias Gram-positivas que pertencem à flora natural da cavidade oral, do aparelho gastrointestinal e urogenital. Pode envolver diversos órgãos. O estudo refere-se à actinomicose pulmonar com envolvimento da parede torácica e compressão medular em um paciente masculino com 29 anos que apresentava febre, tosse, hemoptise e cervicalgia, além de paresia e plegia em membros inferiores com cinco meses de evolução.

Consanguinidade e síndrome de Wolfram: relato de caso / Consanguinity and Wolfram syndrome: case report

JUSTIFICATIVA E OBJETIVOS: A síndrome de Wolfram (SW) é uma condição neurodegenerativa rara, progressiva e de herança autossômica recessiva, envolvendo o sistema nervoso central, nervos periféricos e tecidos neuroendócrinos. Este estudo teve por objetivo relatar um caso de SW. RELATO DO CASO: Paciente do sexo masculino, 17 anos, admitido com quadro de retenção urinária, parestesias e fortes dores nos membros inferiores. Era portador de diabetes mellitus (DM) tipo 1 mal controlado negativo para anticorpos anti-GAD e anti-insulina e apresentava história familiar de consanguinidade, além de dois irmãos com DM. Durante sua avaliação, constataram-se presença de amaurose com atrofia óptica, redução da acuidade auditiva, baixa estatura, atraso puberal, distúrbios psiquiátricos e diabetes insipidus. Foi tratado de infecção urinária, porém apresentou piora súbita aos 35 dias de internação com quadro de crises convulsivas, hipotensão, insuficiência respiratória e óbito. CONCLUSÃO: O diagnóstico de SW deve ser considerado em pacientes com DM associado à atrofia do nervo óptico.

BACKGROUND AND OBJECTIVES: Wolfram syndrome (WS) is a rare, progressive, autosomal recessive neurodegenerative disorder, involving the central nervous system, peripheral nerves and neuroendocrine tissues. This study aimed to reporta case of WS. CASE REPORT: A male patient, aged 17, was admitted with signs of urinary retention, paresthesias and severe pain in the lower limbs. He also had poorly controlled type 1 diabetes mellitus (DM) negative for anti-GAD and anti-insulin and had a family history of consanguinity, and two brothers with DM. During his assessment, he was found to have amaurosis with optic atrophy, decreased hearing acuity, short stature, delayed puberty, psychiatric disorders and diabetes insipidus. He was treated for urinary infection, but suddenly worsened at 35 days of hospital admission, with seizures, hypotension, respiratory failure and death. CONCLUSION: The diagnosis of WS should be considered in patients with DM associated with atrophy of the optic nerve.

Agranulocitose induzida por dapsona em paciente com hanseníase: relato de caso / Dapsone-mediated agranulocytosis in a patient with leprosy: case report

JUSTIFICATIVA E OBJETIVOS: A dapsona é um medicamentode uso amplo, entre os quais se inclui o tratamento da hanseníase. A agranulocitose é descrita como uma reação adversa desse medicamento, embora seja rara e imprevisível. O objetivo deste estudo foi relatar um caso de agranulocitose induzida por dapsona em paciente com hanseníase.RELATO DO CASO: Paciente do sexo feminino, 56 anos, admitida no pronto-atendimento, com história e exame físico compatíveis com amigdalite com início há quatro dias, bem como dor torácica e dispneia. Estava em tratamento de hanseníase com clofazimina e dapsona havia dois meses. O hemograma revelava anemia (hemoglobina = 9,3 g%), leucopenia (800/mm3 - 1% segmentados, 98% linfócitos e 1% monócitos) plaquetopenia (144.000/mm3), e reticulocitose (2,5% ou 87.750/mm3). Os exames de imagem não demonstraram alterações. Diante do quadro, foi suspenso o tratamento com dapsona e realizado antibioticoterapia por via venosa e terapia com fator estimulador de colônia de granulócitos. A paciente teve melhora clínica significativa,recebendo alta no 20° dia de internação hospitalar para acompanhamento ambulatorial.CONCLUSÃO: Considerando que o risco de desenvolvimento da agranulocitose é muito pequeno, ele não deve, em geral, ser um fator importante na decisão sobre o uso da dapsona em pacientes com hanseníase. Entretanto, devem-se conhecer suas manifestações e logo que identificada realizar a terapêutica adequada.(AU)

BACKGROUND AND OBJECTIVES: Dapsone is a drug with many uses, including the treatment of leprosy. Agranulocytosisis described as an adverse reaction of this drug, in spite of being rare and unpredictable. This study has the objective of reporting a case of agranulocytosis mediated by dapsone in a patient with leprosy.CASE REPORT: Female patient, 56-year-old, who presented to the emergency department with clinical history and examination suggestive of tonsillitis within 4 days of onset as well as chestpain and dyspnea. She was in treatment of leprosy with clofazimine and dapsone for 2 months. The complete blood count showed anemia (hemoglobin = 9.3 g%), leukopenia (800/mm3 - 1% neutrophil granulocytes, 98% lymphocytes and 1% monocytes) thrombocytopenia (144.000/mm3), and reticulocytosis(2,5% or 87.750/mm3). The imaging studies have not shown anyabnormalities. The treatment with dapsone was withdrawn and it was started therapy with intravenous antibiotics and granulocytecolony-stimulating factor. The patient had significant clinical improvement,and was discharged for outpatient treatment in the 20th day of hospital admission.CONCLUSION: Considering that the risk of developing agranulocytosisis very low, it should not be, usually, an importantfactor for the decision of using dapsone in patients with leprosy.Nonetheless, its manifestations must be known and, as soon as this complication is identified, the adequate therapy must be provided.(AU)

Polipose hiperplásica: relato de caso / Hyperplastic polyposis: case report

A polipose hiperplásica é uma condição rara, caracterizada pela presença de pólipos hiperplásicos múltiplos no cólon. Relata-se o caso de um paciente de 29 anos que apresentou polipose hiperplásica associada a pólipos mistos.

Hyperplastic polyposis is a rare condition, characterized by the presence of multiple hiperplastic polyps in the colon. It is reported a case of a 29-year-old patient who presented hyperplastic polyposis associated with mixed polyps.