making muscle wasting history

CARE AT DIAGONSIS
The specific cause of a medical disorder is called the diagnosis. It is very important to establish the exact diagnosis when DMD is suspected by your doctor. The aim of care at this time should be to provide an accurate diagnosis as quickly as possible. With prompt diagnosis, everyone in the family can be informed about the general course of DMD,
provided with genetic counselling and told of treatment options. Appropriate care can be put in place and ongoing support and education can be provided to the family. Ideally, diagnosis should be performed by a doctor who is a neuromuscular specialist and who can assess the child clinically and can initiate and interpret investigations properly.
Family follow-up and support following diagnosis will often be supplemented by support from genetic counsellors.
IMPORTANT FACTS TO REMEMBER
Getting a diagnosis is an important step so you and your doctor can make plans for your son’s care
Doctors cannot diagnosis DMD using only a CK test. If your son has elevated CK levels, your doctor will need to confirm the diagnosis using genetic testing.
YOU ARE NOT ALONE reach out to your doctor to answer any questions you might have and seek consulations from a genetic counselor.
This is also a time when contact with support group or advocacy organization can be of particular help. You can find list of contacts on www.treat-nmd.eu/ dmdpatientsorganisations

When to suspect DMD
The first suspicions are usually raised by one of the following three signs (even when there is no history of DMD in the family):

PROBLEMS WITH MUSCLE FUNCTION: It is often a family member who notices something is wrong. Boys who have DMD walk later than other boys their own age. They have enlarged calf muscles and have trouble running,
jumping or climbing stairs. They fall easily and may have a tendency to walk on their toes. They may also have a speech delay. One of the classic signs of DMD is what is known as the “Gowers’” manoeuvre or sign, where the boy
has to use his hands and arms to “walk” up his body in order to push himself to an upright position. This is due to weakness in the hips and thigh muscles (see Figure 2).
HIGH LEVELS OF THE MUSCLE PROTEIN CREATINE KINASE (CK) in a blood test. The finding of a high CK level should prompt an urgent referral to a neuromuscular specialist for confirmation of the diagnosis. High levels of CK are seen in people with other kinds of muscle conditions and a high CK alone is not enough to confirm DMD.
HIGH LEVELS OF THE “LIVER ENZYMES” AST AND ALT in a blood test. High levels of these enzymes in the blood are often associated with liver disease, but muscular dystrophies can also cause this elevation. Unexpectedly
high levels of these enzymes without another cause should raise the suspicion that the CK will be high as well and so a diagnosis of muscular dystrophy might be suspected. A liver biopsy is not recommended.
DELAYED SPEECH DEVELOPMENT: Children with DMD often also have some delay in their speech development and sometimes that is the symptom that is first noticed (see Section 10).
Confirming the diagnosis of DMD
DMD is a genetic disease – it is caused by a mutation or change in the DNA for a gene called the dystrophin or DMD gene. The diagnosis has to be confirmed by genetic testing usually on a blood sample, but other tests are also sometimes performed as well. Some background about genetic testing is provided in Box 1.
The tests
1) GENETIC TESTING
Genetic testing is always necessary even if DMD is first confirmed by muscle biopsy. Different types of genetic tests are able to provide specific and more detailed information about the change in the DNA or mutation. Having genetic confirmation of the diagnosis is important for several reasons. It will help to determine if the boy may be eligible for a
number of mutation-specific clinical trials and will help the family with decisions related to prenatal diagnosis and future pregnancies.
Once the exact mutation or change in the DNA in the dystrophin gene is known, mothers should be offered the opportunity for genetic testing to check whether they are carriers or not. This information will be important for other female family members on the mother’s side (sisters, daughters, aunts,
cousins) to understand if they may be carriers as well.
Genetic testing and a referral to a genetic counsellor will help the family understand the
results of the testing and the potential impact on other family members (see Box 1).
2) MUSCLE BIOPSY ANALYSIS
Your doctor may recommend a muscle biopsy (taking a small sample of muscle for analysis). The genetic mutation in DMD means the body cannot produce the protein dystrophin, or doesn’t produce enough of it. Tests on the muscle biopsy can provide information on the amount of dystrophin present in the muscle cells. If confirmation of the diagnosis has already been achieved by genetic testing, a muscle biopsy may not be required. However, at some centres, the diagnosis of DMD may be made by muscle biopsy analysis. Genetic testing after a positive biopsy diagnosis of DMD is still essential to determine the specific change in the DNA or genetic mutation causing DMD.
There are two types of tests normally performed on a muscle biopsy. They are immunocytochemistry and immunoblotting for dystrophin. These tests are done to determine the presence or absence of dystrophin and can help to distinguish DMD from a milder form of the condition.

3) OTHER TESTS
In the past, the tests known as electromyography (EMG) and nerve conduction studies (needle tests) have been a
traditional part of the assessment of a child with a suspected neuromuscular disorder. The experts agree that these tests are NOT appropriate or necessary for the evaluation of DMD.

Box 1
Why genetic testing is important
Genetic counseling and carrier testing

• Sometions the genetic mutations causing DMD arises by chance in a boy. This is considered a spontaneous mutation in other causes it is passed on by the boys mother.

*If the mother has the mutation, she is called a carrier and can pass it on to her other children. The boy she passes on to will be affected by DMD, whilst girls will be carriers themselves, if the mother tested and found to have the mutuation, she can make informed decisions about future pregnancies, and her female relatives(sisters, aunts, daughters) can also be tested to see if they are also at risk of having a boy with DMD.

• Even when a woman is not a carrier, there is a small risk to future pregnancies because the mutuations may occur in the ova or egg cells. This is called germ line mosacism.

• A carrier also has a small risk of developing a weak heart or even leg weakness later in life. Knowing carrier statues helps to identify this risk so the women can get proper advice.

*You should have access to a genetic counselor who can explain all this to you in more detail.

Eligibility for clinical trials: there are a number of clinical trials underway in DMD that are targeted to certain types of mutations. Genetic testing is important to understand whether your boy is eligible to participate in these trials. To help doctors find the boys who might eligible, you should register in the patient registry.
*The most important question you need to have answered is whether the genetic testing performed was up to currently accepted standards, allowing to exact mutation to be defined. If it was not, then further testing might be required be required. You should discuss with your doctor. The exact mutation is also needed to register with one of the DMD register. You can find details of the kinds of tests that might be done and how effective they are at detecting the absolute detail of the mutations.
*All of the national patient registries for DMD across the world are listed at: www.treat-nmd.eu/patient registries.