Glycogen storage disease type IIIa in curly-coated retrievers.
BACKGROUND
Inborn errors of metabolism impose a significant genetic burden on purebred dogs and cats. The glycogen storage diseases are a category of such disorders that are typed by enzyme analysis, but deoxyribonucleic acid (DNA) based carrier tests are needed for definitive, noninvasive diagnosis and to prevent at-risk matings.


OBJECTIVE
Glycogen storage disease type IIIa (GSD IIIa) is caused by a mutation of the glycogen debranching enzyme gene (AGL) in Curly-Coated Retrievers (CCR).


METHODS
Two CCR exhibiting episodic exercise intolerance, collapse, and lethargy, and related dogs were studied.


METHODS
Structure and amount of glycogen isolated from tissue biopsy specimens was determined by enzymatic digestion, and activities of enzymes of glycogen metabolism were measured. The 33 AGL coding exons and flanking splice sites of an affected dog were amplified by polymerase chain reaction and sequenced.


RESULTS
Debranching enzyme activity was undetectable in liver and skeletal muscle of affected dogs, and accumulated glycogen had absent or short outer chains of alpha1, 4-linked glucose. A single adenosine (A) deletion in AGL exon 32 of affected dog genomic DNA predicted a frame-shift and truncation of the protein product by 126 amino acid residues. The mutation was homozygous in affected dogs and heterozygous in both parents. In addition, the deletion mutation was heterozygous in 16 or not detected at all in 31 related but clinically normal CCR.


CONCLUSIONS
GSD IIIa in CCR is an autosomal recessive trait caused by mutation of AGL. A DNA sequence-based carrier test was developed, and carriers were identified in the United States, New Zealand, Australia, and Finland.
Gregory
Brittany L
BL
Laboratory of Comparative Medical Genetics, Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Shelton
G Diane
GD
Bali
Deeksha S
DS
Chen
Yuan-Tsong
YT
Fyfe
John C
JC
D000818:Animals; D004283:Dog Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease; D006010:Glycogen Storage Disease Type III / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D008099:Liver / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D010375:Pedigree