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Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr 329 Ser mutation in the glycogen‐branching enzyme gene
Author(s) -
Lossos Alexander,
Meiner Zeev,
Barash Varda,
Soffer Dov,
Schlesinger Ilana,
Abramsky Oded,
Argov Zohar,
Shpitzen Shoshi,
Meiner Vardiella
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440604
Subject(s) - glycogen storage disease , gene , allele , mutation , gene mutation , phenotype , biology , tay sachs disease , endocrinology , genetics , medicine , microbiology and biotechnology , glycogen , disease
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 mutatins 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 Tyr 329 Ser 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.