Download Metabolic Genetic Disease Screening Program Pamphlet

Significance of Studies
Identifying new genetic diseases causing inborn errors
of metabolism in animals is of greatest importance for
veterinarians, breeders and individual pet owners.
Precise diagnosis can help in predicting a clinical
course and prognosis, as well as potentially identifying
a specific treatment beyond supportive care. Once
identified, biochemical and molecular tests can be
developed to screen animals at risk for disease, and
carriers with the goal of controlling the disease in the
population. This ability is of considerable benefit for the
breeder and the breed.
Furthermore, some of the affected animals may serve
as new models of human disease in which to better
characterize the disease process and to assess
efficacy and safety of novel therapies including gene
transfer.
While the Metabolic Genetic Screening Laboratory
focuses on disorders in dogs and cats it is also
accepting samples from other species including nonhuman primates and zoo animals.
Specimens:
Urine (free catch) for metabolic tests
Serum for metabolic and enzyme tests
EDTA whole blood for DNA and enzyme tests
Others, depending on suspected disease
Routine CBC, chemistry panel, urinalysis and other
appropriate screening tests should be performed before
submission and results included with submission.
Online submission forms and charges, as well as
sample collection and shipping instructions can be
obtained at http://www.vet.upenn.edu/penngen. The
decision of which patient should have a metabolic
screening is based on the clinical information provided
by the client or veterinarian, and our capability of
testing. This service is offered for a nominal fee.
Supported in part by the National Institutes
of Health NIH-RR02512.
October 2008
Professional Staff at PennGen
Urs Giger, PD Dr med vet MS
Charlotte Newton Sheppard Professor
Director, Metabolic Genetics Laboratory
Mark E. Haskins, VMD, PhD
Professor of Pathology & Medical Genetics
Principal Investigator of NCRR grant
Margret L. Casal, Dr med vet PhD
Assistant Professor of Medical Genetics
James Rhodes, VMD
Resident in Medical Genetics
Mark Thomsen, BS
Research Specialist
Angie Erat, BS MS
Research Specialist
Ulana Prociuk
Research Specialist
Susan Scheerbaum
Administrative Coordinator
METABOLIC GENETIC DISEASE
SCREENING PROGRAM
School of Veterinary Medicine
University of Pennsylvania
Philadelphia
Consultants at the University of Pennsylvania
For Further Information Contact
David Bennett, PhD MD
Director Metabolic Lab
Children Hospital of Philadelphia
Peter J. Felsburg, VMD, PhD
Trustee Professor of Immunology
University of Pennsylvania
Paula S. Henthorn, PhD
Professor of Medical Genetics
Petra Werner, Dr med vet
Assistant Professor of Medical Genetics
Dr. Urs Giger / PennGen
As well as many other colleagues at the University of
Pennsylvania and at other specialized institutions
School of Veterinary Medicine
University of Pennsylvania
Metabolic Genetics Lab/4027 VHUP
School of Veterinary Medicine
University of Pennsylvania
3900 Delancey St.
Philadelphia, PA 19104-6010
Telephone:
FAX:
(215) 898-8894 Office
(215) 573-7545 Lab
(215) 573 2162
Email: [email protected]
http://www.vet.upenn.edu/penngen
Mission of the Metabolic Genetic
Screening Laboratory
The Metabolic Genetic Screening Laboratory at the
University of Pennsylvania tests for many known and
suspected novel hereditary diseases in animals and
thereby provides a resource to veterinarians and breeders
in the diagnosis of inborn errors of metabolism.
Inborn errors of metabolism, or inherited metabolic
diseases, include all biochemical disorders due to
genetically determined single gene defects. They have
gained notable interest and importance during the past
decades. In the field of veterinary medicine more than
900 and 200 inherited disorders have been described in
dogs and cats, respectively, and several new defects are
recognized each year. Breeders have reported that
approximately 10-20% of purebred dogs and cats die
during the first year and some are due to inborn errors of
metabolism.
The mission of the Metabolic Screening Laboratory in the
Section of Medical Genetics of the Ryan Veterinary
Hospital at the University of Pennsylvania is to provide
tests and expertise to diagnose, prevent, and where
possible, treat these diseases. The typical clinical signs of
inborn errors of metabolism include neonatal death, failure
to thrive, growth retardation, corneal clouding, chronic
vomiting or diarrhea, anorexia, neurological signs,
hepatosplenomegaly, skeletal abnormalities and/or facial
dysmorphia. Any animals showing any of these or other
specific signs are candidates for screening. Genetic
metabolic screening includes analyses of specific amino
acids, organic acids, and carbohydrates (such as
glycosaminoglycans and oligosaccharides) in urine, serum
and other fluids or tissues. In the case of metabolic
storage diseases, storage of inappropriate substances
occurs in tissues of affected animals due to enzyme
deficiencies in certain metabolic pathways.
The most useful specimens to examine are urine samples,
because the kidneys cannot reabsorb the abnormal
metabolites. Plasma or serum can also be useful for
further metabolic studies. For several genetic disorders
specialized enzyme studies on specific samples are
required. Finally for quite a few disorders the molecular
defect has been determined and mutation-based breedspecific DNA tests on cheek brushes or EDTA blood
samples can be used to reach a definitive diagnosis.
Urine Metabolic Tests (Examples)
Heparin sulfate:
MPS IIIA: Wirehaired Dachshund, New Zealand
Huntadog
MPS IIIB: Schipperke, (Emu)
Chondroitin sulfate: found in urine of many juvenile
dogs and cats also with
Rapid growth and dwarfism
Congenital hypothyroidism
Metabolic bone disease
Increased Urinary Amino Acid Disorders
Fanconi Syndrome: Basenji and other breeds
Cystinuria: Many dog breeds, Maned wolf, and serval
Hyperornithinemia: Cats
Hypersarcosinemia: Portuguese water dog
Liver disease and Portosystemic shunt: Many dog
breeds and cats
Decreased Urinary Amino Acid Disorders
Taurine deficiency: Cats
“Sick” cat, malnutrition (no Felinine present): Cats
Urinary Organic Acid Disorders
Cobalamin Malabsorption: Giant Schnauzers, Border
Collie, Beagle, Australian Shepherd, and Komodor
Methylmalonic Aciduria: Shar pei, Basset hound, cats
Lactic Acidosis: Many breeds dogs and cats
Mitochondrial myopathy: Old English Sheepdog and
Cocker Spaniel
Fanconi Syndrome: Basenji, Norwegian Elkhound, and
others
Primary hyperoxaluria: Tibetan Spaniel, cats
DNA Based Screening Tests (Breed-specific)
Urinary Carbohydrate Disorders
Diabetes Melitus: Many dog breeds and cats
Renal Glucosuria: Norwegian Elkhounds
Fanconi Syndrome: Basenji and others
Lactosuria: Nursing animals
Liver Disease: Many dog breeds and cats
Urinary Glycosaminoglycan Associated Disorders
Dermatan sulfate:
MPS I: Plotthound, Rottweiler, and cats
MPS VI: Min. Pincher, Min. Schnauzer, Welsh Corgi,
and Domestic and Siamese cats
MPS VII: German Shepherd, Mix breed dog, and cats
Cobalamin Malabsorption: Giant Schnauzer, Australian
Shepherd
Cystinuria (Type I): Newfoundland and Labrador
Factor VII deficiency: Beagle, Alaskan Klee Kai, and
Scottish Deerhound
Factor XI deficiency: Kerry Blue Terrier
Fucosidosis: English Springer Spaniel
Glycogenosis (GSD) type IV: Norwegian Forest cat
Juvenile cardiomyopathy: Portuguese water dog
Mucolipidosis II: Cats
Mucopolysaccharidosis (MPS)
MPS IIIB: Schipperke
MPS VI: Min. Pinschers, Min. Schnauzer, and
Domestic and Siamese cats
MPS VII: German Shepherd
Myotonia congenita: Miniature Schnauzer
Phosphofructokinase (PFK) deficiency: English
Springer Spaniel, American Cocker Spaniel, Whippet
and mixed breed dog
Pyruvate kinase (PK) deficiency: Abyssinians, Somalis,
DSH cat, Beagle, Dachshund, Chihuahua, Eskimo toy,
Basenji, Cairn Terrier and West Highland White Terrier
Severe combined immunodeficiency (SCID): Bassett
Hounds, Welsh Corgis
Hematologic and Other Tests
Special blood compatibility issues:
Feline blood typing (AB, Mik)
Canine DEA 1.1 and Dal typing
Coombs’ and crossmatch (prearranged)
Platelet studies (prearranged)
Erythrocyte osmotic fragility (prearranged)
Immunologic studies (prearranged)
Karyotype (chromosomal analysis, prearranged)
Sry test (male specific gene, prearranged)