ML II (I-Cell disease) and ML III (Pseudo-Hurler Polydystrophy)

What causes this disease?

There is a continuous process in thebody of replacing used materials and breaking them down for disposal. This activity takes place in a special part of the body’s cells called the lysosome. Substances known as enzymes which are 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 to them so the enzymes cannot get to the right place and are lost outside the cell.

The enzyme responsible for attaching the targeting signal is phospho-N-acetylglucosamine-transferase. Although originally thought to be two separate diseases, ML II and ML III are both caused by deficiencies of this targeting enzyme and are thus variations of the same disease. Individuals with more severefeatures have ML II; those with less severe, or attenuated, features have ML III.

The incompletely broken down carbohydrates remain stored in cells in the body causing progressive damage. The cells filled with storage material are known as “inclusion cells,” hence the name “I-Cell” disorder. In some cases babies may show little sign of the disease, but as more and more cells become damaged, symptoms start to appear.

How common are these diseases?

These diseases are very rare and sometimes misdiagnosed, so it is difficult to give accurate figures on frequency. The current estimate is that 2 or 3 individuals per one million births are diagnosed with ML II and ML III.

How is the disease inherited?

We all have all the genes inherited from our parents which control whether we are tall, short, fair, etc. Some genes we inherit are “recessive,” that is to say we carry the gene but it does not have an effect on our development. I-Cell and Pseudo-Hurler syndrome are caused by a recessive gene. If an adult carrying the abnormal gene marries another carrier there will be a one in four chance with every pregnancy that the child will inherit the defective gene from each 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. They can be reassured, however, that as the disease is so rare, the chance of marrying another carrier is very slight provided they do not marry a cousin or other close family member.

Is there a cure?

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.

All families of affected children should seek further information from their doctor or from a Genetic Counselor.