A novel SCARB2 mutation in progressive myoclonus epilepsy indicated by reduced β-glucocerebrosidase activity.
Action myoclonus renal failure (AMRF) syndrome is a rare form of progressive myoclonus epilepsy with renal dysfunction related to mutations in the SCARB2 gene. This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease. We report a family with myoclonic epilepsy, ataxia and skeletal muscle atrophy but without cognitive impairment or overt renal disease. A novel SCARB2 mutation was indicated by a striking discrepancy between lymphocyte and fibroblast GC activity in the proband evaluated for possible Gaucher disease. Our findings expand the genetic and phenotypic diversity of AMRF and suggest that low GC activity may present an important biochemical clue to the diagnosis of AMRF.
Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Marsha
M
Zeigler
Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Vardiella
V
Meiner
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
J P
JP
Newman
Department of Neurology, Shaare Zedek Medical Center, Jerusalem, Israel.
Bettina
B
Steiner-Birmanns
Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Ruth
R
Bargal
Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Vivi
V
Sury
Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Getu
G
Mengistu
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Or
O
Kakhlon
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Ina
I
Leykin
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Zohar
Z
Argov
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Oded
O
Abramsky
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. Electronic address: alos@hadassah.org.il.
Alexander
A
Lossos
D000293:Adolescent; D004789:Enzyme Activation / Q000502:physiology; D005500:Follow-Up Studies; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D020191:Myoclonic Epilepsies, Progressive / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D051116:Receptors, Scavenger / Q000235:genetics*
D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D005962:Glucosylceramidase
Action myoclonus renal failure syndrome; Ataxia; Gaucher disease; LIMP2; Progressive myoclonus epilepsy; SCARB2