ABSTRACT
Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.
Subject(s)
Cognition/drug effects , Enzyme Replacement Therapy , Mucopolysaccharidosis VI/therapy , N-Acetylgalactosamine-4-Sulfatase/genetics , Adolescent , Brazil/epidemiology , Child , Child, Preschool , Female , Glycosaminoglycans/urine , Humans , Male , Mucopolysaccharidosis VI/enzymology , Mucopolysaccharidosis VI/pathology , Mucopolysaccharidosis VI/urine , N-Acetylgalactosamine-4-Sulfatase/therapeutic use , Phenotype , Quality of Life , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic use , Severity of Illness IndexABSTRACT
The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.
Subject(s)
Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/ethnology , Brazil/epidemiology , Cross-Sectional Studies , Heterozygote , Homozygote , Humans , Infant, Newborn , Neonatal Screening/methods , Prevalence , Retrospective Studies , White People/statistics & numerical data , beta-Thalassemia/blood , beta-Thalassemia/epidemiology , beta-Thalassemia/ethnologyABSTRACT
O Ministério da Saúde instituiu o Programa Nacional de Triagem Neonatal através da Portaria nº. 822/GM, incluindo a pesquisa das hemoglobinopatias nos recém-nascidos. No Paraná, é realizada pela Fundação Ecumênica de Proteção ao Excepcional. Determinou-se a prevalência da hemoglobina S em homozigose, heterozigose e Sbeta-talassemia no estado. O sangue coletado em papel filtro foi examinado por focalização isoelétrica e cromatografia líquida de alta precisão (HPLC). De janeiro de 2002 a dezembro de 2004, foram triados 548.810 recém-nascidos e detectados 21 recém-nascidos com os resultados FS, dois FSA e/ou FS e quatro FSA. Após exames confirmatórios aos seis meses de idade, 12 foram definidos como anemia falciforme, com prevalência de 2,2:100 mil recém-nascidos; a interação Sbeta-talassemia foi confirmada em quinze (2,7:100 mil recém-nascidos); e 8.321 recém-nascidos foram diagnosticados como heterozigotos para HbS (1.500:100 mil recém-nascidos). A prevalência da HbS no Paraná é menor do que nas regiões Centro-Oeste, Norte e Nordeste do país. Origem étnica da população, óbitos fetais e casamentos preferenciais podem estar contribuindo para não haver maior número de homozigotos no estado. A interação Sbeta-talassemia sugere presença de povos euro-mediterrâneos na miscigenação dessa população.
The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.
