Department of Neurology, Columbia University Medical Center, New York, New York2Unidad de Enfermedades Neuromusculares, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Instituto de Biomédicina de Sevilla, Consejo Superior de Investigación.
Department of Neurology, Columbia University Medical Center, New York, New York.
JAMA Neurol. 2014 Jan;71(1):41-7. doi: 10.1001/jamaneurol.2013.4888.
The neuromuscular presentation of glycogen branching enzyme deficiency includes a severe infantile form and a late-onset variant known as adult polyglucosan body disease. Herein, we describe 2 patients with adult acute onset of fluctuating neurological signs and brain magnetic resonance imaging lesions simulating multiple sclerosis. A better definition of this new clinical entity is needed to facilitate diagnosis.
To describe the clinical presentation and progression of a new intermediate variant of glycogen branching enzyme deficiency and to discuss genotype-phenotype correlations.
DESIGN, SETTING, AND PARTICIPANTS: Clinical, biochemical, morphological, and molecular study of 2 patients followed up for 6 years and 8 years at academic medical centers. The participants were 2 patients of non-Ashkenazi descent with adult acute onset of neurological signs initially diagnosed as multiple sclerosis.
Clinical course, muscle and nerve morphology, longitudinal study of brain magnetic resonance imaging, and glycogen branching enzyme activity and GBE1 molecular analysis.
Molecular analysis showed that one patient was homozygous (c.1544G>A) and the other patient was compound heterozygous (c.1544G>A and c.1961-1962delCA) for GBE1 mutations. Residual glycogen branching enzyme activity was 16% and 30% of normal in leukocytes. Both patients manifested acute episodes of transient neurological symptoms, and neurological impairment was mild at age 45 years and 53 years. Brain magnetic resonance imaging revealed nonprogressive white matter lesions and spinocerebellar atrophy similar to typical adult polyglucosan body disease.
GBE1 mutations can cause an early adult-onset relapsing-remitting form of polyglucosan body disease distinct from adult polyglucosan body disease in several ways, including younger age at onset, history of infantile liver involvement, and subacute and remitting course simulating multiple sclerosis. This should orient neurologists toward the correct diagnosis.
糖原分支酶缺乏症的神经肌肉表现包括一种严重的婴儿型和一种称为成人多聚糖体病的迟发性变异型。在此，我们描述了 2 例以波动的神经症状和模拟多发性硬化症的脑磁共振成像病变为特征的成人急性发作的患者。需要更好地定义这种新的临床实体，以促进诊断。
描述糖原分支酶缺乏症的一种新的中间变异型的临床表现和进展，并讨论基因型-表型相关性。
设计、地点和参与者：对 2 名非阿什肯纳兹血统的患者进行了临床、生化、形态学和分子研究，在学术医疗中心进行了 6 年和 8 年的随访。这 2 名患者为成人急性发作的神经症状，最初被诊断为多发性硬化症。
临床过程、肌肉和神经形态、脑磁共振成像的纵向研究、糖原分支酶活性和 GBE1 分子分析。
分子分析显示，1 名患者为纯合子（c.1544G>A），另 1 名患者为复合杂合子（c.1544G>A 和 c.1961-1962delCA）GBE1 突变。白细胞中糖原分支酶活性分别为正常的 16%和 30%。两名患者均表现出急性短暂性神经症状发作，45 岁和 53 岁时神经功能缺损较轻。脑磁共振成像显示非进行性白质病变和与典型成人多聚糖体病相似的脊髓小脑萎缩。
GBE1 突变可引起早发性成年发病的复发性多聚糖体病，与成人多聚糖体病在几个方面不同，包括发病年龄较小、婴儿期肝受累史、亚急性和缓解性病程模拟多发性硬化症。这应该使神经科医生能够正确诊断。
