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.

An index for evaluating results in paediatric cardiac intensive care.

OBJECTIVE: To determine if in-hospital mortality after cardiac surgery can be predicted, in children, using a new clinical and surgical index. STUDY DESIGN: Observational, retrospective, cross-sectional. METHODS: We reviewed 818 charts from children undergoing surgery between January, 2000, and December, 2004. The index was calculated by summing the scores from five variables, specifically age, nutritional state, the presence of associated clinical risk factors, surgical complexity, and use and time of cardiopulmonary bypass. Each variable was subdivided into categories of low, medium or high risk, with scores attributed as zero, one or two, respectively. Risks for death were calculated using the odds ratio. RESULTS: Our overall mortality was 14.7%, with our proposed index correlating strongly with mortality (p less than 0.0001). No patients died with scores of zero, but mortality increased from around 10% with a score of three, to close to 30% with scores of five and six, and to over 50% with a score of eight. No patients reached scores of 10, and more than three-fifths of all patients had scores between zero and three. We observed higher mortalities independently for each variable in association with the highest risk scores. CONCLUSIONS: We found that surgery undertaken in the neonatal period, weight below the 5th percentile, the presence of associated clinical risk factors, operations of higher complexity, and more than 90 minutes of cardiopulmonary bypass were all significantly associated with mortality. Our suggested new index showed a linear correlation with mortality, and in our current experience, has proved a valuable tool for predicting adverse outcomes.

Efeito terapêutico da música em crianças em pós-operatório de cirurgia cardíaca / The therapeutic effects of music in children following cardiac surgery

OBJETIVO: Verificar de forma objetiva e subjetiva o efeito da música em crianças no pós-operatório de cirurgia cardíaca em uma unidade de terapia intensiva cardiopediátrica, em conjunto com ações da prática convencional. MÉTODOS: Ensaio clínico aleatorizado por placebo, no qual foram avaliadas 84 crianças, com faixa etária de 1 dia a 16 anos, nas primeiras 24 horas de pós-operatório, submetidas a sessão de 30 minutos de musicoterapia, utilizando música clássica e observadas no início e fim das sessões quanto às seguintes variáveis: freqüência cardíaca, pressão arterial, pressão arterial média, freqüência respiratória, temperatura, saturação de oxigênio, além de uma escala facial de dor. Foi considerado o nível de significância estatística de 5 por cento. RESULTADOS: Dos 84 pacientes iniciais, cinco (5,9 por cento) recusaram participar do estudo. O grupo de cardiopatias mais comum foi o de congênitas acianogênicas com shunt E-D (41 por cento intervenção: 44,4 por cento controle). Quanto à avaliação subjetiva através da escala facial de dor e objetiva das freqüências cardíaca e respiratória, observou-se diferença estatisticamente significante entre os dois grupos após a intervenção (p < 0,001, p = 0,04 e p = 0,02, respectivamente). CONCLUSÕES: Observou-se neste estudo uma ação benéfica da música em crianças no pós-operatório de cirurgia cardíaca, através de alguns sinais vitais (freqüências cardíaca e respiratória) e na redução da dor (escala facial de dor). Contudo, existem lacunas a serem preenchidas nesta área, necessitando a realização de estudos mais aprofundados.

The therapeutic effects of music in children following cardiac surgery.

OBJECTIVE: To investigate, both objectively and subjectively, the effect of music on children in a pediatric cardiac intensive care unit following heart surgery, in conjunction with standard care. METHODS: Randomized clinical trial with placebo, assessing 84 children, aged 1 day to 16 years, during the first 24 hours of the postoperative period, given a 30 minute music therapy session with classical music and observed at the start and end of the session, recording heart rate, blood pressure, mean blood pressure, respiratory rate, temperature and oxygen saturation, plus a facial pain score. Statistical significance was set at 5%. RESULTS: Five of the initial 84 patients (5.9%) refused to participate. The most common type of heart disease was acyanotic congenital with left-right shunt (41% of cases: 44.4% of controls). Statistically significant differences were observed between the two groups after the intervention in the subjective facial pain scale and the objective parameters heart rate and respiratory rate (p < 0.001, p = 0.04 and p = 0.02, respectively). CONCLUSIONS: A beneficial effect from music was observed with children during the postoperative period of heart surgery, by means of certain vital signs (heart rate and respiratory rate) and in reduced pain (facial pain scale). Nevertheless, there are gaps to be filled in this area, and studies in greater depth are needed.