کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833184 | 1065789 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Abnormal neurodevelopment has been widely reported in combined methylmalonic aciduria (MMA) and homocystinuria, cblC type (cblC disease), but neurodevelopmental phenotypes in cblC have not previously been systematically studied. We sought to further characterize developmental neurology in children with molecularly-confirmed cblC. Thirteen children at our center with cblC, born since implementation of expanded newborn screening in New York State, undertook standard-of-care evaluations with a pediatric neurologist and pediatric ophthalmologist. At most recent follow-up (mean age 50Â months, range 9-84Â months), of twelve children with early-onset cblC, three (25%) had a history of clinical seizures and two (17%) meet criteria for microcephaly. A majority of children had hypotonia and nystagmus. Twelve out of thirteen (92%) underwent neurodevelopmental evaluation (mean age 41Â months; range 9-76Â months), each child tested with standardized parental interviews and, where possible, age- and disability-appropriate neuropsychological batteries. All patients showed evidence of developmental delay with the exception of one patient with a genotype predictive of attenuated disease and near-normal biochemical parameters. Neurodevelopmental deficits were noted most prominently in motor skills, with relative preservation of socialization and communication skills. Nine children with early-onset cblC underwent magnetic resonance imaging and spectroscopy (MRI/MRS) at mean age of 47Â months (range 6-81Â months); common abnormalities included callosal thinning, craniocaudally short pons, and increased T2 FLAIR signal in periventricular and periatrial white matter. Our study further characterizes variable neurodevelopmental phenotypes in treated cblC, and provides insights into the etiopathogenesis of disordered neurodevelopment frequently encountered in cblC. Plasma homocysteine and MMA, routinely measured at clinical follow-up, may be poor predictors for neurodevelopmental outcomes. Additional data from large, prospective, multi-center natural history studies are required to more accurately define the role of these metabolites and others, as well as that of other genetic and environmental factors in the etiopathogenesis of the neurologic components of this disorder.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 110, Issue 3, November 2013, Pages 241-247
Journal: Molecular Genetics and Metabolism - Volume 110, Issue 3, November 2013, Pages 241-247
نویسندگان
James D. Weisfeld-Adams, H. Allison Bender, Anna Miley-Ã
kerstedt, Tamiesha Frempong, Nina L. Schrager, Keyur Patel, Thomas P. Naidich, Victoria Stein, Jessica Spat, Stephanie Towns, Melissa P. Wasserstein, Inga Peter, Yitzchak Frank, George A. Diaz,