Medium-term open label trial of L-carnitine in Rett syndrome
ABSTRACT Treatment strategies in Rett syndrome so far have been essentially symptomatic and supportive. In order to establish the medium-term effects of L-carnitine, an open label trial was performed in a cohort of 21 Rett syndrome females, with a control group of 62 Rett syndrome females of a similar age, for a 6-month period. Compared with the Rett syndrome controls, treatment with L-carnitine led to significant improvements in sleep efficiency (P=0.027), especially in the subjects with a baseline sleep efficiency less than 90%, energy level (P<0.005) and communication skills (P=0.004). There was no significant difference in the subject's level of physical activity, hand function or in the quality of life of the subject's parents. In addition, before and after comparisons of the treatment group showed improvements in expressive speech (P=0.011). Treatment with L-carnitine seems to be of significant benefit in a subgroup of girls with Rett syndrome. In these girls, small but discernible improvements may be of considerable importance to their parents and carers.
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ABSTRACT: Rett syndrome (RTT) is a devastating neurodevelopmental disorder that affects one in ten thousand girls and has no cure. The majority of RTT patients display mutations in the gene that codes for the methyl-CpG-binding protein 2 (MeCP2). Clinical observations and neurobiological analysis of mouse models suggest that defects in the expression of MeCP2 protein compromise the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function, such as insulin-like growth factor 1 (IGF1), are good candidates for ameliorating the symptoms of RTT. IGF1 and its active peptide, (1-3) IGF1, cross the blood brain barrier, and (1-3) IGF1 ameliorates the symptoms of RTT in a mouse model of the disease; therefore they are ideal treatments for neurodevelopmental disorders, including RTT. We performed a pilot study to establish whether there are major risks associated with IGF1 administration in RTT patients. Six young girls with classic RTT received IGF1 subcutaneous injections twice a day for six months, and they were regularly monitored by their primary care physicians and by the unit for RTT in Versilia Hospital (Italy). This study shows that there are no risks associated with IGF1 administration.06/2012; 2012:679801. DOI:10.1155/2012/679801
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ABSTRACT: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes. To describe the variation in phenotype in Rett syndrome using four different scales, by means of a population database. Using multiple sources of ascertainment including the Australian Paediatric Surveillance Unit, the development of an Australian cohort of Rett syndrome cases born since 1976 has provided the first genetically characterised population based study of Rett syndrome. Follow up questionnaires were administered in 2000 to families and used to provide responses for items in four different severity scales. A total of 199 verified cases of Rett syndrome were reported between January 1993 and July 2000; 152 families provided information for the follow up study. The mean score using the Kerr scale was 22.9 (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17 years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and ranged from 18 to 75. We have expanded on the descriptive epidemiology of Rett syndrome and shown different patterns according to the severity scale selected. Although all affected children are severely functionally dependent, it is still possible to identify some variation in ability, even in children with identified MECP2 mutations.Archives of Disease in Childhood 02/2003; 88(1):38-43. DOI:10.1136/adc.88.1.38 · 2.91 Impact Factor
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ABSTRACT: The association of Rett syndrome with pathogenic mutations of the methyl-CpG binding protein 2 (MECP2) gene was first made in 1999. Since that time, it has been found that the clinical phenotype can, at least in part, be explained in terms of the type and location of the MECP2 mutation and epigenetic factors such as skewing of X-chromosome inactivation. In addition, MECP2 mutations may be associated with non-Rett syndrome clinical phenotypes, including nonsyndromic and syndromic X-linked mental retardation and Angelman-like phenotypes. Intense research efforts are currently focused on understanding the pathogenesis of Rett syndrome, using sophisticated techniques such as microarray analysis, and the development of mouse models, with an ultimate aim being the development of targeted therapies that could ameliorate or even prevent the devastating consequences of this enigmatic neurodevelopmental disorder.Journal of Child Neurology 11/2003; 18(10):669-74. DOI:10.1177/08830738030180100901 · 1.67 Impact Factor