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Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial(More)
Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the "giant" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin, and our analysis of(More)
OBJECTIVES Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in(More)
Although linked with cardiac dysfunction, the association of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and pulmonary artery hypertension (PAH) has not been previously described. PAH and right ventricular heart failure were identified by echocardiography in a 3-year-old boy with a history of hypotonia,(More)
BACKGROUND Tissues with high energy demands, such as the heart, are susceptible to the effects of mitochondrial DNA point mutations. OBJECTIVE To investigate the frequency of Wolff-Parkinson-White (WPW) syndrome among a phenotypically and genotypically homogeneous cohort of patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike(More)
OBJECTIVE To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. METHODS We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort(More)
OBJECTIVE To characterize the short-term course of spinal muscular atrophy (SMA) in a genetically and clinically well-defined cohort of patients with SMA. DESIGN A comprehensive multicenter, longitudinal, observational study. SETTING The Pediatric Neuromuscular Clinical Research Network for SMA, a consortium of clinical investigators at 3 clinical(More)
OBJECTIVE To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning. METHODS We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months.(More)
BACKGROUND AND PURPOSE Cerebral vasodilatory capacity (CVC) testing with transcranial Doppler has been shown to be useful in the assessment of stroke risk in patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis and occlusion, but whether hemodynamic status improves, deteriorates, or remains the same over time is uncertain. (More)
Body composition is sparsely described in spinal muscular atrophy (SMA). Body (BMI, mass/height in m(2)), fat-free (FFMI, lean mass/height in m(2)) and fat (FMI, fat mass/height in m(2)) mass indexes were estimated in 25 children (aged 5-18) with SMA (2 type I, 13 type II, 10 type III) using dual-energy radiograph absorptiometry and anthropometric data(More)