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Mak and colleagues discover the molecular basis of a rare form of severe dysbetalipoproteinemia and determine the effects of complete absence of apoE on neurocognitive and visual function and on lipoprotein metabolism. Whole-exome sequencing was performed on the patient’s DNA. Despite complete absence of apoE, the patient had normal vision, exhibited normal cognitive, neurological, and retinal function, had normal findings on brain magnetic resonance imaging, and had normal cerebrospinal fluid levels of β-amyloid and tau proteins. Despite a profound effect on lipoprotein metabolism, detailed neurocognitive and retinal studies failed to demonstrate any defects, as highlighted in an editorial by Lane-Donovan and Herz.
Fogel and coauthors investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation were conducted. They identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation, as emphasized in an editorial by Gomez and Das.
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Pascual and colleagues identify the most helpful outcomes for treatment evaluation and uphold (rather than diminish) blood glucose concentration and stimulate the tricarboxylic acid cycle, including anaplerosis, in glucose transporter type I deficiency using the medium-chain, food-grade triglyceride triheptanoin. Supplementation of the regular diet with food-grade triheptanoin was studied. They found that 1 participant (7%) did not manifest spike-waves; however, spike-waves promptly decreased by 70% (P = .001) in the other participants after consumption of triheptanoin.
Holland and coauthors assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. They segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods, and they modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. They report that normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.
Highlights. JAMA Neurol. 2014;71(10):1203. doi:10.1001/jamaneurol.2013.4171