Josephson S A, Schmidt R E, Millsap P, McManus D Q, Morris J C
Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Neurol Sci. 2001 Jul 15;188(1-2):51-60. doi: 10.1016/s0022-510x(01)00546-9.
Kufs' disease is the rare, adult-onset form of the neuronal ceroid-lipofuscinoses (NCL). Two clinical Kufs' phenotypes have been described, one featuring generalized tonic-clonic seizures and the other characterized by dementia. Autosomal dominant inheritance of Kufs' disease has been reported for only two families. The genetic and molecular defects underlying Kufs' disease are unknown. We report a third family with apparent autosomal dominant Kufs' disease in a family of English ancestry. Ten individuals (five men, five women) have been affected over five generations. Age of onset typically is in the fourth decade of life and is heralded by seizures. Clinical and neuropsychological assessments in several affected individuals, however, confirm the presence of dementia and follow-up evaluations suggest that dementia is the primary disabling feature of the illness. Motor abnormalities also are frequent. Neuropathological examination (three cases) documents the presence of neuronal lipopigment accumulation consistent with NCL. The combination of dementia and seizures in this and two other reported families with autosomal dominant Kufs' disease suggest that this entity represents a distinctive clinicopathological entity. Dementia is prominent but is almost always associated with generalized seizures and motoric disturbances early in the disease course. Kufs' disease should be considered in the differential diagnosis of early onset, atypical dementia.
库夫斯病是神经元蜡样脂褐质沉积症（NCL）的一种罕见的成人发病形式。已描述了两种临床库夫斯病表型，一种以全身强直阵挛性发作为主，另一种以痴呆为特征。仅在两个家族中报道过库夫斯病的常染色体显性遗传。库夫斯病的遗传和分子缺陷尚不清楚。我们报告了一个具有明显常染色体显性库夫斯病的英裔家族中的第三个家族。五代中有10人（5男5女）患病。发病年龄通常在生命的第四个十年，以癫痫发作为先兆。然而，对几名受影响个体的临床和神经心理学评估证实存在痴呆，随访评估表明痴呆是该疾病的主要致残特征。运动异常也很常见。神经病理学检查（3例）记录了与NCL一致的神经元脂色素积累。该家族以及另外两个报道的常染色体显性库夫斯病家族中痴呆与癫痫发作的结合表明，这种疾病代表了一种独特的临床病理实体。痴呆很突出，但在疾病早期几乎总是与全身癫痫发作和运动障碍相关。在早发性非典型痴呆的鉴别诊断中应考虑库夫斯病。
