Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI

Background: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme (R), BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.Methods: Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.Results: A significant negative correlation was seen with treatment with ERT and urinary GAG levels. of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.Conclusions: the prescribed dosage of 1 mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population. (C) 2013 Elsevier Inc. All rights reserved.BioMarin Pharmaceutical Inc.ShireGenzymeBioMarinFiocruz MS, Inst Nacl Saude Mulher Crianca & Adolescente Fern, Ctr Genet Med, BR-22250020 Rio de Janeiro, RJ, BrazilUniv Fed Bahia, Serv Genet Med, Salvador, BA, BrazilHosp Albert Sabin, Fortaleza, Ceara, BrazilUniv Fed Mato Grosso do Sul, Fac Med, Campo Grande, MS USAUniv São Paulo, Inst Crianca, São Paulo, BrazilHosp Barao de Lucena, Recife, PE, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilCtr Reabilitacao Infantil, Natal, RN, BrazilHosp Univ Maranhao, Sao Luis, MA, BrazilUniversidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, SP, BrazilHosp São Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, São Paulo, BrazilUniv Fed Rio Grande do Norte, HOSPED, Hosp Pediat Prof Heriberto Ferreira Bezerra, Natal, RN, BrazilUniv Fortaleza, Fortaleza, Ceara, BrazilUniv Fed Rio Grande do Norte, BR-59072970 Natal, RN, BrazilUniv Fed Triangulo Mineiro, Uberaba, MG, BrazilHosp Clin Acre, Rio Branco, AC, BrazilUniv Fed Espirito Santo, HUCAM, Vitoria, ES, BrazilUniversidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, SP, BrazilHosp São Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, São Paulo, BrazilWeb of Scienc

Inalação contínua com fenoterol na criança com asma aguda grave: efeitos clínicos imediatos Continuous fenoterol inhalation by children with severe acute asthma: immediate clinical effects

Objetivos: avaliar as alterações da freqüência cardíaca, da pressão arterial, do psiquismo e da saturação arterial de oxigênio, após a inalação contínua com fenoterol, na criança com asma aguda grave. Casuística e Métodos: foram estudados 30 pacientes com asma aguda grave, atendidos no PAM-Pediatria do Hospital Universitário - UFMS. Os pacientes receberam inalação contínua durante uma hora, com 0,5 mg/kg (2 gotas/kg) de fenoterol. O psiquismo, a saturação arterial de oxigênio, a freqüência cardíaca e a pressão arterial foram avaliados antes, imediatamente após, e uma hora após a inalação com fenoterol. Resultados: 17 crianças eram do sexo masculino (56,6%), e 13 do sexo feminino (43,4%). Foi observado sonolência em 16 (53,3%), agitação psicomotora em 1 (3,3%), náusea e vômito em 12 pacientes (40%). A média da saturação arterial de oxigênio aumentou de 90,9 2,8% para 92,7 2,5% (p<0,05) após a inalação. Houve um aumento estatisticamente significativo da média da freqüência cardíaca do início da inalação ao término da mesma (139,5 13,5 bpm, 166,5 11,1bpm, respectivamente) p<0,05. A média da pressão arterial era de 117,56 10,3 / 74,6 7 mmHg antes da inalação, e ocorreu diminuição ao final da inalação, atingindo valores médios de 107,6 11 / 63,6 9,3 mmHg (p<0,05). Conclusões: a inalação contínua com fenoterol na dose de 0,5 mg/kg, na criança com asma aguda grave, desencadeou sonolência, náusea, vômitos, taquicardia e diminuição da pressão arterial. Os autores sugerem que esta modalidade de tratamento seja realizada com monitorização clínica, em ambiente hospitalar, merecendo atenção especial aquelas crianças com doenças concomitantes, nas quais os efeitos sistêmicos da terapia poderiam ser potencializados pelas doenças subjacentes.<br>Objective: to evaluate the alterations of heart rate, blood pressure, psychological aspects and oxygen saturation after continuous fenoterol inhalation (0.5 mg/Kg) by children with severe acute asthma. Methods: we studied 30 patients with severe acute asthma who were treated at the pediatric ward of Hospital Universitário - UFMS. The patients inhaled 0.5 mg/Kg of fenoterol (two drops/Kg) during one hour. Psychological aspects, oxygen arterial saturation, heart rate and blood pressure were evaluated at three different moments: before, after and one hour after the fenoterol inhalation. Results: there were 17 males (56.6%) and 13 females (43.4%). Sleepiness was observed in 16 (53.3%), psychomotor agitation in one (33%) and nausea and vomiting in 12 patients (40%). The average of oxygen arterial saturation increased from 90.9 &plusmn; 2.8% to 92.7 &plusmn; 2.5% (P<0.05) after inhalation. There was statistically significant increase in the average heart rate before and after inhalation (139.5 &plusmn; 13.5 beats/min, 166.5 &plusmn; 11.1 beats/min, respectively), P<0.05. A significant decrease in blood pressure rate was observed from 117.56 &plusmn; 10.3 / 74.6 &plusmn; 7 mmHg, to 107.6 &plusmn; 11 / 63.6 &plusmn; 9.3 mmHg (P<0.05). Conclusions: continuous fenoterol (0.5 mg/Kg) inhalation by children with severe acute asthma caused sleepiness, nausea, vomits, palpitation and decrease in blood pressure rate. The authors suggest that patients submitted to this treatment need clinical monitorship at hospital settings. Children with concomitant diseases such as diarrhea, vomits, and dehydration require special attention