Background on Type 2 Gauchers

What is Type 2 Gauchers Disease?

From the UK Gauchers Association website, comes the following definition of Type 2 Gauchers Disease:

"Gauchers disease is an inherited disorder. Children with Type 2 lack an important enzyme called glucocerebrosidase. This enzyme deficiency results in the accumulation of a fatty substance (glucocerebroside) which is normally produced during the recycling of cells in the body but is then broken down by the enzyme.

"The human body contains specialised cells called macrophages. Macrophages contain lysosomes where enzymes degrade worn-out cells into simple molecules for recycling. The enzyme glucocerebrosidase is located within the lysosomes and is responsible for breaking down glucocerebroside into glucose and a fat called ceramide.

"Babies with Type 2 Gauchers disease lack the normal form of the glucocerebrosidase enzyme and are unable to break down glucocerebroside. Instead, the glucocerebroside remains stored within the macrophages, preventing them from functioning normally. Enlarged macrophages, containing undigested glucocerebroside, are called Gauchers cells. These cells are the hallmark of the disease and will be found in the bone marrow, spleen, liver and brain.

How does the baby contract it?

If you can possibly think back to high school or university biology, you may remember the term autosomal recessive disorder. The Children's Gaucher Research Fund website (see the Links section) has a section on basic genetics, but what it essentially comes down to is that baby received a defective copy of the glucocerebrosidase gene from both mum and dad. Both parents must be "carriers" (i.e. they have both a 'normal' and 'defective' copy of the gene in their DNA). During conception, they both contribute one part of that particular gene to the baby, either the normal or defective half. Hence, of the four genes (two from each parent) that can be passed on, there is a 25% chance that the defective gene from each parent is contributed to the child (therefore the condition expresses itself). There is a 50% chance that the child will only inherit one copy of the gene (and thus would be considered a "carrier"). And finally, there is a 25% chance that baby will inherit two copies of the perfectly normal gene. See the diagram below for a graphical representation of autosomal inheritance (taken from the Winter 2003-2004 Children's Gaucher Research Fund newsletter).

The important thing to note is that this chance of having a baby with Type 2 Gauchers Disease (25%) applies to each and every pregnancy. Testing is required every time the mother falls pregnant. This test usually involves a CVB (chorionic villus biopsy) at 10 weeks, whereby a sample of the placenta is removed and cultured, and the enzyme levels are measured. Amniocentesis can also be conducted at 14-16 weeks.

It is a conservative estimate that one baby born in every one hundred thousand (1:100,000) has Type 2 Gauchers Disease. When Brannon was ill, I could find no evidence of any other children having the same disease in Australia at that time. I also had email conversations with a representative of Genzyme, who could not recall hearing of a case of Type 2 Gauchers in Australia in the past four years.

What are the symptoms?

Failure to thrive (lack of weight gain)

Backwards tilting of the head (retroflexion)

Squinting (known as 'strabismus')

Hypertonia (stiffness of the limbs and body)

Inability to swallow

Seizures and fitting

Enlarged Liver and Spleen (as per Type 1 symptoms)

Inability to shake colds and chest infections

Note that these symptoms have been listed roughly in the order that they expressed themselves in our son Brannon.

Is there any treatment?

There is no specific treatment or cure for Type 2 Gauchers Disease. The enzyme replacement therapy (ERT) treatment currently in use in Australia is only approved for use in Type 1 and Type 3 patients. I have been given a strong indication that approval for the use of such a drug for Type 2 patients would NOT be approved under any circumstance in this country. ERT has benefits on controlling the systemic symptoms of Type 2 Gauchers (i.e. reducing the enlargement of the liver and spleen). However, there have been cases overseas where cerezyme has been administered to patients with little or no neurological benefit: this included injecting the drug directly into the brain.

What is the prognosis?

Many babies die at around 1 year of age. 90% of cases will die at 2 years. Death often comes as a result of complications arising from chest infections or viral illnesses. Any that survive beyond this point usually have chronic, debilitating symptoms.

Where is the research at now?

From the current (Winter 2003-2004) Children's Gaucher Research Fund newsletter, studies are targeting four areas:

Brain neurons - Understanding the molecular basis of the effects of Gauchers disease on the brain;

Brain locations - Understanding which particular parts of the brain are affected, and matching those affected areas to the types of symptoms expressed by children;

Three-dimensional structure - The structure of the glucocerebrosidase enzyme has been determined, and it may be possible to create an enzyme replacement therapy based on smaller molecules (in order to try and get chemicals past the 'blood-brain' barrier, a major problem in devising effective treatments for the neurological symptoms of Type 2 Gauchers);

Parkinson's Disease - Studies have found that there are similarities in the brains of sufferers of Parkinson's Disease and Type 2 and 3 Gauchers Disease. Advances in one area of research may bring according benefits in the other.