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Gaucher Disease
by Yael Rosenberg, RN
Description
Gaucher disease is an autosomal recessive disorder that is the
result of mutation of the GBA gene located on chromosome 1. It
affects many of the body’s tissues and organs. Also known as
cerebroside lipidosis and familial splenic anemia, this condition
was named for the physician who first described the disease, Dr.
Philippe C. Gaucher.
Gaucher Disease occurs at any age, but it is most dangerous and most
severe in infants. In essence, Gaucher Disease results from the
deposition of glucocerebroside in the liver, bone marrow, and
spleen. The enzyme glucocerebrosidase normally breaks down
glucocerebroside, but patients with Gaucher Disease do not
manufacture enough of the enzyme, and deposition of glucocerebroside
results.
There are 3 major types of Gaucher Disease which are categorized by
researchers according to their characteristic features and age of
onset. (2 others have been identified)
Type I
Also called non-neuropathic since it usually does not affect the
central nervous system, is the most common form of this disorder.
The gene responsible for this type has been mapped to chromosome 1.
The characteristic aspects of this disease range from mild to severe
and may emerge at any point of the patient’s lifetime, though most
patients are diagnosed at age 20.
Type II & III
These types of Gaucher disease are categorized as neuropathic
forms as they cause problems and issues in the central nervous
system. Gaucher disease Type III progresses more slowly than Type
II. Most children who have type II die at age two; while those with
type III develop symptoms during childhood or adolescence.
Perinatal Lethal Form
This type of Gaucher Disease is the most severe form of the
disorder. It causes life-threatening complications beginning before
birth or during infancy. Infants with perinatal lethal form of
Gaucher Disease survive only a few days after birth.
Cardiovascular Type
As the name implies this form of Gaucher Disease affects
primarily the heart, causing the heart valves to calcify.
Symptoms
The symptoms of Gaucher disease type I are extremely variable. Each
person can exhibit a very different clinical course. Some
individuals are mildly affected and have little or no health
problems; others show much more significant problems, either from an
early age or later in life. Some people even develop a progressive
condition; therefore, periodic assessment may be appropriate
throughout a person's lifetime. Symptoms range from mild to severe
and can appear at anytime from infancy to old age. Only 30% of
people who have this type of disease will show symptoms.
Symptoms include:
• Anemia
• Fatigue
• Easy bruising
• Tendency to bleed due to reduced platelets
• Enlarged spleen and liver
• Bone pain (bone crisis)
• Osteoporosis – general demineralization of the bones
• Spontaneous fractures (due to weakening of the bones)
• Arthritis
Type II and III are the rarer types which often present with
neurological problems. In addition to presenting with many of the
symptoms that those with type I have, types II and III can cause
abnormal eye movements, seizures and brain damage.
Perinatal Lethal Form presents with the following symptoms:
• Extensive swelling due to fluid build-up before birth
• Dry scaly skin or other skin abnormalities
• Enlarged liver and spleen
• Distinctive facial features
• Severe neurological issues.
Cardiovascular Type may have the following symptoms
• Hardening of heart valves
• Mild enlargement of spleen
• Bone disease
• Eye abnormalities
Older individuals with all types of Gaucher disease have an
increased risk of developing certain cancers.
Incidence and Carriers
Prevalence of all types in general population: 1 in 50,000 and
100,000
Type I Gaucher disease is the most common genetic disease among Jews
of Ashkenazi heritage.
Carrier frequency: Approximately 1 in 12 in Jewish population; 1 in
100 in the general population in the United States
Disease frequency: Approximately 1 in 500 to 1000 in Ashkenazi
Jewish population; 1 in 40,000 in the general population in the
United States.
Types II and III are not more prevalent among the Jewish population
than any other.
Type III disease frequency is greater in Norrbottnian region of
Sweden 1 per 50,000 population
Treatment
Presently there is no cure for Gaucher disease. A number of people
with type I Gaucher disease have extremely mild symptoms and
therefore do not need to be treated. However there are treatments
typically prescribed for types I and III. Currently there is no
specific treatment for type II.
Treatments for Type I and III
-Enzyme Replacement Therapy (ERT):
This treatment utilizes synthetic (man-made) enzymes which are
administered to the patient in order to replace the deficient
enzymes. The enzyme is injected into the patient every two weeks for
the rest of their life to reduce the accumulation of the detrimental
glucocerebrosides in the body. Results of this therapy have been
varied but it has been most frequently effective for those who have
type I Gaucher disease. Patients receiving ERT have shown a
reduction in the enlargement of the spleen and liver, as well as
resolution of some blood abnormalities. Children receiving this
treatment often exhibit a growth spurt and weight gain.
-Substrate Reduction Therapy (SRT)
For individuals unable to take enzyme replacement therapy, substrate
reduction therapy is the preferred alternative. SRT is given in a
form of oral medication Zavesca which is known to cross the
blood-brain barrier. SRT works by inhibiting the body’s ability to
produce the enzyme responsible for the synthesis of
glucocerebroside. With the decrease in the fatty substances,
glucocerbroside, the lysosomes are able to catch up and eliminate
the excess fatty substance buildup,. SRT has been shown to decrease
the size of the liver and spleen, though other therapeutic responses
were more favorable with ERT. In addition, SRT does cause certain
adverse effects such as; diarrhea, stomach pains, loss of weight and
peripheral neuropathy.
-Bone Marrow Transplantation
A highly risky and very invasive technique, bone marrow
transplantation is currently used only for those with serious cases
of Gaucher disease who cannot receive ERT. In this surgical
procedure, the blood forming cells damaged by Gaucher disease are
taken out and replaced by a healthy donor’s cells. If this technique
is successful it affords the patient a lifelong cure.
-Surgery
Patients may undergo orthopedic surgery if bones and joints are
affected by Gaucher. On rare occasions the spleen may be removed if
patients are unable to receive ERT or the spleen enlargement impedes
other organs.
Testing
Diagnosis: confirmed by blood test for low glucocerebrosidase enzyme
DNA testing detects about 89% - 96% of gene mutations in Ashkenazi
Jews with the disease and can identify carriers.
Prenatal testing for Gaucher disease is done via chorionic villus
biopsy or amniocentesis
For those diagnosed with Gaucher, periodic tests are done to
ascertain progression of the disease. Those include: Dual energy
X-ray absorptiometry that measures bone density, and magnetic
resonance imaging (MRI) to check for spleen and liver enlargement.
Laboratories and Screening
The following laboratories offer genetic testing for Gaucher
disease:
• United States
• Israel
• Canada
• India
• Europe
UNITED STATES
Ambry Genetics
100 Columbia #200
Aliso Viejo, CA 92656
Toll Free (866) 262-7943
Phone (949) 900-5500
Fax (949) 900-5501
ARUP Laboratories
500 Chipeta Way
Salt Lake City, UT 84108-1221
Phone: (800) 522-2787
Fax: (800) 522-2706
Email:
clientservices@aruplab.com
Baylor Medical Genetic Laboratories
Medical Genetics Laboratories
Baylor College of Medicine
One Baylor Plaza, NAB 2015
Houston, TX 77030
Phone: (800) 411-GENE (4363)
Fax: (713) 798-2787
Email: genetictest@bcm.edu
Client Services Manager
Alejandra Quick
Phone: (713) 798-7656
Fax: (713) 798-2787
Email: ahquick@bcm.edu
Boston University School of Medicine- Human Genetics
700 Albany Street
Suite 408
Boston, MA 02118-2394
Phone: (617) 638-7083
Fax: (617) 638-7092
Cincinnati Children's Hospital Medical Center, Division of Human
Genetics
3333 Burnet Avenue,
Cincinnati, Ohio 45229-3039
Phone: (513) 636-4474
Fax: (513) 636-4373
Email:
moleculargenetics@cchmc.org
Denver Genetic Laboratories
UCD DNA Diagnostic Laboratory
12800 East 19th Avenue
Mail Stop 8313
Aurora, CO 80045
Phone: (303) 724-3801 (Main laboratory)
Fax: (303) 724-3802 (HIPAA-secure)
Detroit Medical Center University Laboratories
University Health Center
4201 St. Antoine
Suite 3E-1
Detroit, Michigan 48201
Phone: (313) 993-2631
Fax: (313) 993-2658
Emory University School of Medicine
Emory Molecular Genetics Laboratory
Atlanta, GA
Phone: (404) 778-8500
Fax: (404) 778-8559
Email: eglgc@emory.edu
Genzyme Genetics
Molecular Diagnostic Laboratory
3400 Computer Drive
Westborough, MA 01581
Phone: (508) 898-9001
Fax: (508) 389-5549
Toll Free: (800) 255-7357
Genzyme Genetics General Inquiries:
Phone: (800) 357-5744
Fax: (508) 389-5549
Client Services - Reproductive Genetics
Toll Free: (800) 848-4436
LabCorp
1912 Alexander Drive
Research Triangle Park, NC 27709
Phone: (800) 345-4363
Fax: (919) 361-7798
Email: genetics@labcorp.com
Mayo Medical Laboratories
3050 Superior Drive NW
Rochester, MN 55901
Phone: (800) 533-1710
Phone: (507) 266-5700
Fax: (507) 284-4542
Jewish Genetic Screening Program, New York Methodist Hospital
506 6th St.
Brooklyn, NY 11215
Phone: (718) 780-5799
Mount Sinai Genetic Testing Laboratory (DNA Division)
The Mount Sinai Medical Center
One Gustave L. Levy Place
New York, NY 10029-6574
Phone: (212) 241-3055
Fax: (212) 241-9467
Email:
rochelle.pakier@mssm.edu
New Jersey Medical School
Institute of Genomic Medicine
University Hospital
Director: James J Dermody, PhD, FACMG
150 Bergen Street, F Level,
Room F342
Newark, NJ 07103
Phone: (973) 972-3170
Fax: (973) 972-0795
NYU Langone Medical Center
Human Genetics Program
550 First Avenue, Room MSB 136
New York, NY 10016
Phone: (212) 263-5746
Fax: (212) 263-7590
PreventionGenetics
Molecular Diagnostics and BioBanking
3700 Downwind Drive
Marshfield, Wisconsin 54449 USA
Phone: (715) 387-0484
Fax: (715) 384-3661
Web:
http://www.preventiongenetics.com
Quest Diagnostics-Nichols Institute
Molecular Genetics Laboratory
Medical Director, Charles Strom, MD, PhD
33608 Ortega Highway
San Juan Capistrano, CA 92690
Contact: Joy Redman, MS, Genetic Counselor
Phone: (949) 728-4279
Fax: (949) 728-4874
Seattle Children's Hospital
Department of Laboratories
A-6901
4800 Sand Point Way NE
Seattle, WA 98105
Phone: (206) 987-2617
Fax: (206) 987-3840
Email:
LabClientServices@seattlechildrens.org
ISRAEL
Assaf Harofeh Medical Center
Molecular Genetics Laboratory
Zerifin, Israel
Phone: (+972) 8-977-9617
Web:
http://www.assafh.org/ENG/index.asp
The Bnai Zion Medical Center
The Simon Winter Institute for Human Genetics,
47 Eliyahu Golomb, Haifa , 33394
Phone: (+972)-4-835-9851
Phone: (+972)-4-835-9495
Web: http://www.b-zion.org.il
Carmel Medical Center
Molecular Genetics Laboratory
Michal Street, Haifa 34362
Phone: (+972) 4-8250407
Edith Wolfson Medical Center
Molecular Genetics Laboratory
Holon, Israel
Contact: Esther Leshinsky-Silver, PhD
Phone: (+972) 3- 502- 8692
Fax: (+972) 3- 502- 8543
GGA –Galil Genetic Analysis Ltd
P.O.B. 3664
Kazerin, Hatzafon, Israel 12900
Phone: (+972) 4-900-7100
Fax: (+972) 4-900-7111
Email: gga@gga.org.il
Ha’Emek Medical Center
Molecular Genetics Unit
Afula 18101 , Israel
Phone: (+972)-4-6495416
Email:
morad_kh@clalit.org.il
Kaplan medical center, Molecular Genetics Laboratory
REHOVOT , ISRAEL
Phone: (+972) 8-944-1534
Web:
http://www.clalit.org.il/kaplan
Meir Medical Center
Molecular Genetics Laboratory
Kfar Saba , Israel
Phone: (+972) 9-747-1059
Web:
http://www.clalit.org.il/meir/Content/Content.asp
Meuhedet Rosh Haayin
Molecular Genetics Laboratory.
Hey Beiyar 22 Rosh Haayin 48056 Israel
Phone: (+972)-3-915-5330
Fax: (+972)-3-915-5331
Web: https://www.meuhedet.co.il
Pronto Diagnostic Ltd.
19A Habarzel Street
Ramat Hachayal
Tel Aviv, Israel 69710
Phone: (+972) 73-312-6155
Fax: (+972) 73-212-6144
Email:
info@prontodiagnostics.com
Rabin Medical Center
Molecular Genetics
Petah Tikva, Israel
Director: Mordechai Shohat, MD
Genetic Counselor: Inbal Kedar, MSc
Phone: (+972) 3-937-7659
Fax: (+972) 3-937-7660
Email: inbalkd@clalit.org.il
Rambam Medical Center, Molecular Genetics Laboratory
PO Box 9602 Haifa 31096 Israel
Phone: (+972) 4-854-2456
Tel Aviv Sourasky Medical Center
Genetic Lab
Sourasky Builidng, 1st Floor, Wing 1
Tel Aviv, Israel
Phone: (+972) 3-697-4704
Phone: (+972) 3-697-3992
Fax: (+972) 3-697-4555
Web: http://www.tasmc.org.il
Western Galilee Hospital-Naharia
Molecular Genetics Laboratory
P.O.Box 21
Naharia 2100 Israel
CANADA
Genetrack Biolabs Inc.
Molecular Genetics Laboratory
Vancouver, British Columbia, Canada
Contact: Kevin Chu
Phone: (604) 325-7282
Fax: (604) 325-2208
Email: kevin@genetrack.bc.ca
INDIA
Sir Ganga Ram Hospital
Center of Medical Genetics
New Delhi, Delhi, India
Contact: Renu Saxena, PhD
Phone: (+91) 11-42252139
Fax: (+91) 11-42251034
Email: renu@saxena.com
EUROPE
• Germany
• Netherlands
• Spain
GERMANY
Bioscientia GmbH
Center for Human Genetics
Ingelheim, Germany
Contact: Dr. Nadine Bachmann
Phone: (+49) 6132-781-429
Fax: (+49) 6132-781-194
Email:
nadine.bachmann@bioscientia.de
Diagenom GmbH
Robert-Koch-Str. 10
D-18059 Rostock
Germany
Phone: (+49) 381 7022750
Fax: (+49) 381 7022759
Email: mail@diagenom.de
Dr. Eberhard and Partner
MVZ Dortmund
Dortmund, Nordrhein-Westfalen, Germany
Phone: (+49) 231-95720
Fax: (+49) 231-579834
Email: genetik@labmed.de
NETHERLANDS
Academic Medical Centre, University of Amsterdam
DNA Diagnostics Laboratory
Amsterdam, Netherlands
Contact: Marcel M.A.M. Mannens, PhD
Phone: (+31) 205667899
Fax: (+31) 2056699689
Email: kg dna@amc.uva.nl
SPAIN
IMEGEN (Instituto de Medicina Genómica, S.L.)
Science Park. University of Valencia
C/ Catedrático Agustín Escardino, 9
E46980 Paterna (Valencia)
SPAIN
Phone: (+34) 963 212 340
Fax: (+34) 963 212 341
Email: info@imegen.es
Resources and more
The Comprehensive Gaucher Treatment Center
9090 Wilshire Blvd., Suite 200
Beverly Hills, CA 90211
Phone: 310-888-8680
Phone: (888) 248-4456
Fax: (310) 285-7298
Email:
info@gaucherwest.com
Dr. Harry Dunn
Gaucher Program
Phone: (518) 786-7723
Children’s Gaucher Research Fund
Website:
http://www.childrensgaucher.org
Gaucher’s Association
25 West Cottages
London NW6 IRJ
UK
Phone: (+ 44) 171 433 1121
Email: support@gaucher.net
National Gaucher Foundation, Inc.
11140 Rockville Pike
Suite 350
Rockville, MD 20852
Toll Free: (800) 925-8885
Phone: (301) 816-1515
Gaucher’s Southeast Treatment Center
Phone: (954) 721-4720
Website:
http://www.gauchersoutheast.com
Support Groups
International Collaborative Gaucher Group (ICGG) Gaucher
Registry
Web:
http://www.lsdregistry.net/gaucherregistry
United States & Other Non-European Countries
Gaucher Registry
Genzyme Corporation
500 Kendall Street
Cambridge, MA 02142
USA
Toll Free: (800) 745-4447, x15500
Latin America
Gaucher Registry
Genzyme do Brasil Ltda.
Praça Floriano, 19 - 26° Andar - Centro
20031-050 Rio de Janeiro - RJ
Phone: (+55) 21-2156-9989
Email:
help@gaucherregistry.com
Europe
Gaucher Registry
Genzyme Europe BV
Gooimeer 10
1411 DD Naarden
The Netherlands
Phone: (+31) 35-699-1232
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