Mucolipidosis Type IV (ML4) - Jewish Genetic Disease

Description
Mucolipidosis Type IV is an autosomal recessive genetic disorder that is the result of the mutation of the MCOLN1 gene located on chromosome 19. Mucolipidosis type IV (ML4) was first described in 1974, its gene independently discovered by Dr. Bach of Hadassah Medical Center in Israel. ML4 is one of the lysosomal storage diseases in which there is inability of the cells to produce certain enzymes required for breakdown of specific compounds. In this disease both lipids and mucopolysaccharides are not broken down and therefore accumulate in the cells disrupting their normal function. This disorder affects the brain and the nervous system. Onset of this disease is usually the first year of life. Life expectancy is approximately 45 years of age.

Symptoms
Children with ML4 begin to exhibit cognitive and motor developmental delay during the first year of life. Though most cases are severe, motor and mental retardation can be mild in some cases. Visual acuity may be normal at the beginning but is progressively impaired by corneal clouding and retinal degeneration. Other symptoms include: hypotonia –poor muscle tone, pseudo-strabismus – false cross eyes.

Incidence and Carriers
Carrier Frequency: 1 in 100 to 1 in127 in Ashkenazi Jews

Disease Frequency: 1 in 40,000. Approximately 70% of those affected with this disorder are Jewish of Ashkenazi descent.

Treatment
At present, no specific therapy is available. Optimal supportive care, including physical, occupational and speech therapy, can significantly improve the function and quality of life of affected children. Families with affected children should seek genetic counseling and be offered the option of prenatal diagnosis for future pregnancies.

Testing
Diagnosis: The name, ML4 was given since it has similar diagnostic storage bodies noted in every cell as do the mucopolysaccharide and lipid storage diseases. A diagnosis of ML4 should be contemplated with mentally retarded Jewish children presenting with corneal clouding. Conjuctival biopsies done show characteristic storage bodies and thus confirm the diagnosis.

Parents are encouraged to have their child examined and tested for ML4 if they exhibit the following symptoms associated with ML4;

- Prominent developmental delays in gross motor skills, such as sitting, standing and walking;
- Significant delays in fine motor skills, such as holding a cup or crayon; Marked speech delays;
- Vision problems caused by corneal clouding, retinal degeneration. Child exhibits sensitivity to light, and seems cross eyed.

Currently a simple blood test can be done to diagnose ML4. Additionally the blood test will identify significantly diminished gastrin (stomach acid) levels which are common in children with ML4.

Carrier screening test is available to ascertain the presence of a gene mutation associated with Mucolipidosis Type IV

Prenatal diagnosis for ML4 : CVS (Chorionic Villus Sampling) or Amniocentesis

Laboratories and Screening
The following laboratories offer genetic testing for Canavan Disease:
   • United States
   • Israel
   • Canada
   • Europe

UNITED STATES
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

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

GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone: (301) 519-2100
Fax: (301) 519-2892

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
Tel: (800) 848-4436

Hartford Hospital
Clinical Lab Partners/Molecular Genetics and Cytogenetics
Newington, CT
Phone: (860) 545-3409
Fax: (860) 545-3733

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

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

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

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

UCLA Diagnostic Molecular Pathology Laboratory
11633 San Vicente Blvd.,
Los Angeles, CA 90049
Phone: (310) 794-2781
Fax: (310) 794-2765

UC – San Diego Medical Genetics
University of California San Diego
Division of Medical Genetics (MC 0639)
9500 Gilman Dr.
La Jolla, CA 92093-0639
Phone: (858) 534-3093
Fax: (858) 534-0269
Email: tcahill@ucsd.edu

The Victor Center for Jewish Genetic Diseases
Albert Einstein Medical Center
5501 Old York Road, Levy 2 West
Philadelphia, PA 19141
Phone: (215) 456-8722

Victor Outreach and Screening Program for Ashkenazi Jewish Genetic Diseases
Floating Hospital for Children at Tufts Medical Center
800 Washington Street, Box 340
Boston, MA 02111
Phone: (617) 636-7721
Web: www.tuftsnemc.org/OurServices/SpecialServicesandCenters/JewishGeneticDiseasesScreening

Victor Center for Jewish Genetic Diseases at
University of Miami Miller School of Medicine
Address: Clinical Research Building
1120 NW 14th Street - 8th Floor
Miami, FL 33136
Phone: (305) 243-4524
Deborah Zimbalist Wasserman, M.S.
Genetic Counselor/Coordinator
Mobile: (786) 897-9587
Email: DWasserman@med.miami.edu

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, (+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

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

Hadassah Hospital Hadassah Ein Karem
Human Molecular Genetic Laboratory
Dr. Israela (Issy) Lerer (Director)
POB 12000
Jerusalem 91120
Israel
Phone: (+972) 2- 677-6016
Fax : (+972) 2- 677-7499
Web: http://www.hadassah.org.il

Ha’Emek Medical Center
Molecular Genetics Unit
Afula 18101 , Israel
Phone: (+972) 4-649-5416
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
Prof. Ruth Gershoni -Baruch
E-mail: rgershoni@rambam.health.gov.il

Sheba Medical Center
The Danek Gertner Institute Human Genetics
Molecular diagnosis Laboratory
Tel Hashomer; Ramat Gan . 52621, Israel
Phone: (+972)3-530-3060
Web: http://www.eng.sheba.co.il

Soroka University Medical Center
Genetics Laboratories
Beer-Sheva, Israel
Telephone: (+972)- 8-6400258
Web: http://www.clalit.org.il/soroka/Content/Content.asp?CID=43&u=420

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
The Hospital for Sick Children
Molecular Genetics Division
555 University Avenue
Room 3420, Hill Wing
Toronto, ON M5G 1X8 Canada
Phone: (416) 813-7200 ext. 1
Fax: (416) 813-7732

Procrea
Division of Opmedic Group Inc.
1361 Beaumont Avenue
Suite 301
Mont-Royal (Quebec)
H3P 2W3
Phone: (514) 345-8535
Toll Free: 1 888 PROCREA
Contact: France Lagace
Phone: (514) 345-8535 ext 2234
Fax: (514) 345-8978
Email: flagace@procrea.com

EUROPE
• Germany

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

Centogene GmbH
Schillingalee 68
18057 Rostock
Germany
Phone: (+49) 381-203652-0
Fax: (+49) 381-203652-19
Email: office@centogene.com

Resources and More
National MPS Society, Inc.
17 Kraemer Street
Hicksville, New York 11801
Phone: (516) 931-6338
Fax: (516) 822-2041
Web: http://www.mpssociety.org

Support Groups
Randy Yudenfriend
President, ML4 Foundation
MUCOLIPIDOSIS IV FOUNDATION
719 East 17th Street
Brooklyn, New York 11230
Toll Free: (877) ML4-5459
Phone: (718) 434-5067
Web: http://www.ml4.org

National Mucopolysaccharidoses/Mucolipidoses Society (MPS), Inc
PO Box 736
Bangor ME 04402-0736
Phone: 207-947-1445
Fax: 207-990-3074
Email: info@mpssociety.org
Web: http://www.mpssociety.org

Society for Mucopolysaccharide (MPS) Diseases
MPS House Repton Place White Lion Road
Amersham HP7 9LP
United Kingdom
Phone: (+44) 0845 389 9901
Email: mps@mpssociety.co.uk
Web: http://www.mpssociety.co.uk