Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up

Mucopolysaccharidosis type II (MPS II - Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans, affecting multiple organs and systems. Enzyme replacement therapy does not cross the blood brain barrier, limiting results in neurological forms of the disease. Another option of treatment for severe MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS type I, since it can preserve neurocognition when performed early in the course of the disease. To date, only few studies have examined the long-term outcomes of HSCT in patients with MPS II. We describe the seven-year follow-up of a prenatally diagnosed MPS II boy with positive family history of severe MPS form, submitted to HSCT with umbilical cord blood cells at 70 days of age. Engraftment after 30 days revealed mixed chimerism with 79% donor cells; after 7 years engraftment remains at 80%. I2S activity 30 days post-transplant was low in plasma and normal in leukocytes and the same pattern is observed to date. At age 7 years growth charts are normal and he is very healthy, although mild signs of dysostosis multiplex are present, as well as hearing loss. The neuropsychological evaluation (Wechsler Intelligence Scale for Children - Fourth Edition - WISC-IV), disclosed an IQ of 47. Despite this low measured IQ, the patient continues to show improvements in cognitive, language and motor skills, being quite functional. We believe that HSCT is a therapeutic option for MPS II patients with the severe phenotype, as it could preserve neurocognition or even halt neurodegeneration, provided strict selection criteria are followed

Atenção aos defeitos congênitos no Brasil: panorama atual Birth defects and health strategies in Brazil: an overview

O impacto dos defeitos congênitos no Brasil vem aumentando progressivamente, tendo passado da quinta para a segunda causa dos óbitos em menores de um ano entre 1980 e 2000, apontando para a necessidade de estratégias específicas na política de saúde. Foram localizadas, no Brasil, direcionadas aos defeitos congênitos, ações governamentais e não-governamentais. Estas envolvem serviços de informação sobre agentes teratogênicos na gravidez e sobre doenças metabólicas geneticamente determinadas, monitorização de defeitos congênitos, programa de triagem neonatal e tratamento de algumas doenças genéticas, imunização contra rubéola, além da fortificação de farinhas com ácido fólico como ação preventiva de certos defeitos congênitos. Apesar da importância de tais iniciativas, é pouco provável que seja possível atender à questão dos defeitos congênitos de forma integrada. Para a efetivação de um sistema de atenção voltado aos defeitos congênitos, deverá ser formulada política específica, de âmbito nacional, com a participação ativa do Ministério da Saúde, utilizando, como espinha dorsal, os serviços de genética existentes. Só assim, será possível a estruturação de uma rede regionalizada, hierarquizada e funcional voltada à atenção aos defeitos congênitos no Brasil.<br>Birth defects have increased progressively in Brazil, shifting from the fifth to the second cause of infant mortality from 1980 to 2000, thus highlighting the need for specific health policy strategies. Some governmental and nongovernmental actions related to birth defects in Brazil include information services on teratogenic agents and inborn errors of metabolism, monitoring of birth defects, neonatal screening and treatment of some genetic diseases, and rubella immunization. In addition, flour fortification with folic acid for prevention of certain birth defects has begun recently. Despite the importance of such initiatives, it is still difficult to view birth defects from a comprehensive perspective. A specific national policy on birth defects must be formulated. Active participation is needed by the Ministry of Health, using existing genetic services as the backbone, in order to develop a regionalized, hierarchical, and functional network related to birth defects in Brazil

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2001/00422-5]Genzyme Corporatio