ML II and ML III (I-Cell Disease and Pseudo-Hurler Polydystrophy
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Overview
Although originally thought to be two separate diseases, ML II and ML III are both caused by deficiencies of a targeting enzyme and are variations of the same disease. Individuals with more severe features have ML II; those with less severe, or attenuated, features have ML III.
At present there is treatment for symptoms as they arise but no cure for the underlying condition. Various experimental methods have been used to try to replace the missing enzyme, but none so far has been of any significant long term benefit.
These diseases are very rare and sometimes misdiagnosed, so it is difficult to give accurate figures on frequency. The current estimate is that two or three individuals per 1 million births are diagnosed with ML II and ML III.
Understanding the Cause of MPS and ML
The body constantly replaces used materials and breaks them down for disposal. This activity happens in the lysosomes of the cells. Enzymes responsible for breaking down the used materials can only reach the lysosome after a special signal has been attached to them. In ML II and ML III, the signal is not attached and the enzymes fail to reach the cell. The enzyme responsible for attaching the targeting signal is phospho-N-acetylglucosamine-transferase. The cells filled with storage material are known as “inclusion cells,” hence the name “I-Cell” disorder. Babies may show little sign of the disease, but as cells sustain damage, symptoms start to appear.
Understanding the Inheritance of the Disease
I-Cell and Pseudo-Hurler syndrome are caused by a recessive gene. There is a one in four chance with every pregnancy that the child will inherit the variant gene from each carrier parent and will be affected with the disease. There is a two in three chance that unaffected brothers and sisters of an individual with ML will be carriers.
Common Questions
What are the differences in ML II, II/III, and III?
ML II (Mucolipidosis II or I-cell disease) is the most severe form, with early onset and rapid progression, causing significant developmental delays and multiple organ involvement. ML II/III is an intermediate form with later onset and slower progression, while ML III (also called pseudo-Hurler polydystrophy) is milder, with symptoms often appearing in childhood or adolescence, primarily affecting bones and joints.
How do I know which type my child has?
Diagnosis is based on clinical evaluation, enzyme testing, and genetic analysis. Your metabolic specialist will review symptoms, laboratory results, and genetic testing to determine the specific type of ML your child has.
What can we do for symptom management?
Symptom management focuses on supportive, multidisciplinary care. This may include physical and occupational therapy, orthopedic care for joint and bone issues, respiratory support, and regular monitoring of cardiac and neurological health. While there is currently no cure, early intervention and coordinated care can improve quality of life and help manage symptoms effectively.
Clinical Trials
Clinical trials are research studies that determine whether treatments or devices are safe for humans. These studies also look for effective medical approaches for specific conditions and help provide reliable data for patients, researchers and doctors. Clinical trials are conducted on small groups to determine whether a drug or procedure causes negative reactions or unsatisfactory side effects.
HSCT
Hematopoietic stem cell transplantation is a blood stem cell transplant. Possible sources of blood stem cells include bone marrow, peripheral blood and umbilical cord blood.
To date, HSCT represents a therapy with a relatively short but effective track record for ML II (I-cell disease.) Patients ages 0.3-1.7 have been transplanted at the University of Minnesota. Results have shown good cardiopulmonary function in two patients while one has developed pulmonary hypertension. All children remain mildly to moderately neurodevelopmentally delayed.
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