Lossos A, Meiner Z, Barash V, Soffer D, Schlesinger I, Abramsky O, Argov Z, Shpitzen S, Meiner V
Department of Neurology, Hebrew University-Hadassah Medical School and Hadassah University Hospital, Jerusalem, Israel.
Ann Neurol. 1998 Dec;44(6):867-72. doi: 10.1002/ana.410440604.
Adult polyglucosan body disease (APBD) is a late-onset, slowly progressive disorder of the nervous system caused by glycogen branching enzyme (GBE) deficiency in a subgroup of patients of Ashkenazi Jewish origin. Similar biochemical finding is shared by glycogen storage disease type IV (GSD IV) that, in contrast to APBD, is an early childhood disorder with primarily systemic manifestations. Recently, the GBE cDNA was cloned and several mutations were characterized in different clinical forms of GSD IV. To examine whether mutations in the GBE gene account for APBD, we studied 7 patients from five Jewish families of Ashkenazi ancestry. The diagnosis was based on the typical clinical and pathological findings, and supported by reduced GBE activity. We found that the clinical and biochemical APBD phenotype in all five families cosegregated with the Tyr329Ser mutation, not detected in 140 controls. As this mutation was previously identified in a nonprogressive form of GSD IV and was shown in expression studies to result in a significant residual GBE activity, present findings explain the late onset and slowly progressive course of APBD in our patients. We conclude that APBD represents an allelic variant of GSD IV, but the reason for the difference in primary tissue involvement must be established.
成人多葡聚糖体病（APBD）是一种迟发性、缓慢进展的神经系统疾病，由阿什肯纳兹犹太裔患者亚组中的糖原分支酶（GBE）缺乏引起。糖原贮积病IV型（GSD IV）也有类似的生化表现，与APBD不同的是，GSD IV是一种主要表现为全身症状的儿童早期疾病。最近，GBE cDNA被克隆，并且在GSD IV的不同临床形式中鉴定了几种突变。为了研究GBE基因突变是否与APBD有关，我们研究了来自五个阿什肯纳兹犹太裔家庭的7名患者。诊断基于典型的临床和病理表现，并得到GBE活性降低的支持。我们发现，在所有五个家庭中，临床和生化APBD表型与Tyr329Ser突变共分离，在140名对照中未检测到该突变。由于该突变先前在非进行性GSD IV形式中被鉴定，并且在表达研究中显示导致显著的残余GBE活性，目前的研究结果解释了我们患者中APBD的迟发性和缓慢进展过程。我们得出结论，APBD代表GSD IV的等位基因变体，但必须确定主要组织受累差异的原因。
