RESUMO
Disease course of feeding difficulties in spinal muscular atrophy type 2 is not well documented. Disease-modifying therapies rapidly change the trajectory of motor function and survival in spinal muscular atrophy, but effects on co-morbidities like bulbar function are unknown. We analysed data concerning feeding problems and their standard of care treatment in 146 patients with spinal muscular atrophy type 2. Data were collected from two separate cohorts: one single-centre retrospective chart review study from the United Kingdom (London), and one prospective questionnaire-based multicentre study from Italy. Cumulatively feeding difficulties were present in 88 patients (60%) in these 2 cohorts. Median age at onset of problems was 6.5years (range 0-16.5 years). Eighty-two patients (60%) showed periods of underweight according to age adjusted body mass index, and thirty-six patients (25%) showed malnourishment with a significant drop on their weight curves. Enteral feeding was indicated in 23 out of 72 patients in the UK cohort (32%) because of weight loss, oropharyngeal dysphagia or aspiration. Gastrostomy and its placement was generally well tolerated, uncomplicated in 96%, never reversed and performed without Nissen fundoplication in 66% of patients. After gastrostomy chest infections improved in 80% and nutritional status (e.g., Body Mass Index) in 84% of patients. These results show that feeding difficulties are a common problem in spinal muscular atrophy type 2. Treatment strategies should be tailor-made on the symptoms and needs of the individual patient.
Assuntos
Transtornos de Deglutição/fisiopatologia , Atrofias Musculares Espinais da Infância/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Itália , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e Questionários , Reino Unido , Adulto JovemRESUMO
AIM: Assessment of the efficacy of vitamin D replenishment and maintenance doses required to attain optimal levels in boys with Duchenne muscular dystrophy (DMD). METHOD: 25(OH)-vitamin D levels and concurrent vitamin D dosage were collected from retrospective case-note review of boys with DMD at the Dubowitz Neuromuscular Centre. Vitamin D levels were stratified as deficient at <25â nmol/L, insufficient at 25-49â nmol/L, adequate at 50-75â nmol/L and optimal at >75â nmol/L. RESULT: 617 vitamin D samples were available from 197 boys (range 2-18â years)-69% from individuals on corticosteroids. Vitamin D-naïve boys (154 samples) showed deficiency in 28%, insufficiency in 42%, adequate levels in 24% and optimal levels in 6%. The vitamin D-supplemented group (463 samples) was tested while on different maintenance/replenishment doses. Three-month replenishment of daily 3000â IU (23 samples) or 6000â IU (37 samples) achieved optimal levels in 52% and 84%, respectively. 182 samples taken on 400â IU revealed deficiency in 19 (10%), insufficiency in 84 (47%), adequate levels in 67 (37%) and optimal levels in 11 (6%). 97 samples taken on 800â IU showed deficiency in 2 (2%), insufficiency in 17 (17%), adequate levels in 56 (58%) and optimal levels in 22 (23%). 81 samples were on 1000â IU and 14 samples on 1500â IU, with optimal levels in 35 (43%) and 9 (64%), respectively. No toxic level was seen (highest level 230â nmol/L). CONCLUSIONS: The prevalence of vitamin D deficiency and insufficiency in DMD is high. A 2-month replenishment regimen of 6000â IU and maintenance regimen of 1000-1500â IU/day was associated with optimal vitamin D levels. These data have important implications for optimising vitamin D dosing in DMD.
Assuntos
Corticosteroides/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
If the risk of disease is not the same for all germline mutations in a given gene, or if there are other familial modifiers of risk in carriers, then family-history-based estimates of average risk for detected mutations in that gene will depend on how carriers are sampled. Risk may also depend on the site or type of mutation. We studied 51 families with strong histories of breast cancer who attended Australian family cancer clinics and in which a germline mutation in BRCA1 or BRCA2 had been identified (28 and 23 families, respectively). Breast cancer risk in carriers was estimated under maximum likelihood theory, using information from all family members including those not tested, with adjustment for ascertainment by conditioning on genotype of the proband and family phenotype. The average cumulative risk of breast cancer for mutations in either BRCA1 or BRCA2 was 27% (95% confidence interval 16-43%) to age 50 and 64% (44-83%) to age 70. When grouped, the incidence in carriers was on average 17 (10-30) times that in non-carriers, independent of gene or mutation type (hazard ratios: 11 (4-29) for BRCA1, 23 (12-43) for BRCA2 (P for difference = 0.23); 13 (6-29) for protein-truncating mutations, 30 (9-104) for missense mutations and 30 (10-90) for splice-site mutations). For missense mutations, this was equivalent to a cumulative risk to age 70 of 83% (40-100%) and was due in part, but not totally, to the missense mutations 300 T>G in BRCA1 and 4486 G>T in BRCA2, which were individually found to be associated with high risk (P<0.001). Mutations in the central region of BRCA1 may be associated with a lower risk. The issue of the pathogenicity of specific variants may be addressed analytically providing there are one or more suitably informative families with that mutation.