Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Frequencies of CCR5-D32, CCR2-64I and SDF1-3'A mutations in Human Immunodeficiency Virus (HIV) seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia

ABSTRACT: The distribution of genetic polymorphisms of chemokine receptors CCR5-D32, CCR2-64I and chemokine (SDF1-3 A) mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1) seropositive individuals (seropositive group) and 139 seronegative individuals (seronegative group) from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-D32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3 A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.

Avaliação clínica de doadores de sangue portadores do vírus linfotrópico de células T humanas (HTLV - I/II)

Os vírus linfotrópicos de células T humanas do tipo I e II (HTLV-I/II) são retrovírus que podem ser transmitidos por transfusão de sangue. Estes vírus estão associados com paraparesia espástica tropical (PET), leucemia/linfoma de células T do adulto (L/LTA) e outras doenças sistêmicas imunomediadas. O presente estudo teve como objetivo investigar sinais clínicos de patologias associadas a esses vírus para utilizar na triagem clinica de candidatos à doação de sangue. Usou procedimentos padronizados para avaliação clinica de 30 doadores de sangue soropositivos para HTLV-I/II confirmados pela técnica de reação em cadeia da polimerase (PCR) matriculados no ambulatório do Núcleo de Medicina Tropical da UFPA. Paralelamente, através de interrogatório clínico complementar, estudou grupo controle com 40 candidatos à doação de sangue escolhidos aleatoriamente, que tiveram resultados sorológicos negativos. Dos 30 pacientes examinados, verificou-se que 23 eram portadores de HTLV-I e 07 HTLV-II. Na avaliação clínica, 15 pacientes (50%) não referiram queixas, sendo que 12 pacientes com queixas exclusivamente neurológicas. Observou 05 pacientes com formigamentos; 05 com diminuição da força muscular; 04 com constipação intestinal; 02 com parestesia; 02 com nódulos subcutâneos; 01 com incontinência urinária; 01 com visão borrada; 01 com diminuição do libido. No grupo controle, 05 candidatos (12,5%) referiram queixas. Os resultados indicam que diminuição da força muscular e formigamento devem ser questionados na triagem clínica prévia à doação de sangue para reduzir risco de infecção transfusional.