Mucolipidosis Type IV (ML4)
by Yael Rosenberg, RN

   •  Description
   •  Symptoms
   •  Incidence and Carriers
   •  Treatment
   •  Testing
   •  Resources and More
   •  Support Group

Description
Mucolipidosis type IV (ML4), first described in 1974, is the most recently recognized Jewish genetic disease. 

Mucolipidosis Type IV is an autosomal recessive disorder, mainly seen in Jews of Eastern European background. It is a cation channel disorder that is characterized by severe neurological and ophthalmologic abnormalities. ML4 usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones. Children with ML4 typically reach a maximum developmental age of 15 months in language and motor function, although their receptive abilities are more advanced. Children diagnosed with ML4 experience retinal degeneration that severely limits their vision. There is currently no treatment for this tragic disorder.

Symptoms
Children with ML4 begin to exhibit developmental delay during the first year of life. Many parents seek ophthalmologic evaluations for pseudo-strabismus. Motor and mental retardation ranges from mild to severe. The earliest sign is corneal clouding; however, approximately 30% of patients develop clouding between three and five years of age. Other eye findings may include pseudostrabismus (false appearance of crossed eyes) and/or retinal degeneration, which may lead to blindness in later years. There is no gross involvement of the skeletal system nor urinary mucopolysaccharide excretion. Patients currently range from one to 45 years of age. Prognosis and life expectancy beyond the latter age is unknown. Recently, a few very mildly affected children with ML4 have been diagnosed. This raises the possibility of other undiagnosed mildly involved patients.

The only way to know if your child has ML4 is to have your child examined and tested by a doctor.

As a parent, you can observe whether your child has the following symptoms commonly associated with ML4 and generally appearing in the first year:
   •  Pronounced developmental delays in gross motor skills, such as sitting, standing and walking;
   •  Pronounced developmental delays in fine motor skills, such as holding a cup or crayon;
   •  Pronounced developmental delays in speech;
   •  Vision problems of corneal clouding, retinal degeneration, sensitivity to light, and strabismus; and,
   •  Low muscle tone (hypotonia).

If you observe these symptoms, tell you child’s doctor.

Incidence and Carriers
One in 100 Ashkenazi Jews is a carrier.
The disease frequency is unknown.

The disease is transmitted through heredity. Both parents have to carry the mutated gene for there to be a possibility of transmission to their child.
If both are carriers:
   •  There is a One in Four chance that the child will inherit the mutated gene from each parent and have the disease
   •  There is a One in Four chance that the child will inherit normal genes from both parents and be completely free of the disease.
   •  There is a Two in Four chance the child will inherit one of a mutated gene from one parent and a normal gene from the other parent, and in this case, be a carrier like the parents, but free of the disease.

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, derives from the presence of diagnostic storage bodies (cytoplasmic inclusions seen under electron microscope) in almost every cell of these patients. The storage bodies are similar to those observed in the mucopolysaccharide and lipid storage diseases; thus the designation mucolipidosis. The diagnosis should be considered in retarded Jewish children who have corneal clouding. The electron microscopic demonstration of characteristic storage bodies in a conjunctival biopsy supports the clinical diagnosis.

There is a carrier screening test which requires a sample of blood that can determine whether or not there is a gene mutation present for Mucolipidosis Type IV

Prenatal diagnosis for ML4 can be attained with the use of CVS (Chorionic Villus Sampling) or Amniocentesis, which are performed early in the pregnancy.

How can my child be tested?
There is now a simple blood test to diagnose ML4. The blood test will also detect very low gastrin (stomach acid) levels which are common in children with ML4.

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

DNA Direct, Inc.
Pier 9 - Suite 105
San Francisco, CA 94111 USA

Phone: 415-646-0222
Fax: 415-646-0224

For Genetic Counseling and Screening Resources – Click Here

Support Groups
Randy Yudenfriend
President, ML4 Foundation
MUCOLIPIDOSIS IV FOUNDATION
719 East 17th Street
Brooklyn, New York 11230
718-434-5067
Website: 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 
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 
http://www.mpssociety.co.uk