For Healthcare Providers

Care for people living with Duchenne includes a multidisciplinary team of professionals providing coordinated, comprehensive care. While the Duchenne Care Considerations offer details of the surveillance and management of each medical subspecialty area of care, PPMD has additional tools and resources that may be helpful to you. Please let us know if there are tools and/or resources that you do not see, that you feel might be helpful.

Diagnosing Duchenne

Signs and Symptoms of Duchenne

Identifying neuromuscular diagnoses can be difficult. The signs may be subtle variants of normal behavior and development, and may be hard to discern. PPMD worked with the Center for Disease Control and Prevention (CDC) to develop ChildMuscleWeakness.org, a tool to enable medical professionals to recognize the possible signs of neuromuscular disorders and to seek diagnosis.

In Duchenne muscular dystrophy, signs and symptoms often begin in early infancy. Delayed milestones such as sitting, walking and talking are the most noticeable, but there are other signs and symptoms as well. Learn more about the signs and symptoms of Duchenne.

If your family is still in the observation stage, the American Academy of Pediatrics has developed the Physical Developmental Delays: What To Look For tool to help parents know if and when to seek additional advice and testing for their child.

How to Diagnose Duchenne

• Order a CK: If you have any suspicion that your patient may have gross motor or speech delay, draw a CK.
• Genetic testing: If an elevated CK is discovered, the second step in diagnosis is genetic testing, which is the best way to obtain exact genetic information for a conclusive Duchenne diagnosis. This can be initiated by either the primary care provider or before/after a referral to a pediatric neurologist familiar with Duchenne (for a list of PPMD Duchenne Care Centers, click here). PPMD has a genetic testing program called Decode Duchenne that provides free genetic testing and counseling eligible individuals.
• Elevated liver enzymes: due to the metabolism by the liver of muscle breakdown that occurs in Duchenne, liver enzymes in this disease (AST, ALT) are always elevated.  These elevated enzymes are indicative of Duchenne, not of liver dysfunction. For this reason, further evaluation of liver function (i.e., liver biopsy, referral) in generally not necessary.

Supporting a Diagnosis of Duchenne

Delivering difficult diagnoses is, well, difficult. PPMD has developed some tools that we hope will be helpful.

• Delivering the Diagnosis: PPMD convened a meeting of parents and professionals to discuss suggestions for professionals to assist in delivering this diagnosis to families, and to begin to help families adapt to this devastating diagnosis. The resulting summary article from this meeting, Facilitating family adjustment to a diagnosis of Duchenne, may be helpful for you.
• Materials for Families: We know that this devastating diagnosis is stressful for parents. To help relieve that stress, and to give parents enough, but not too much information, we have a section on the PPMD website specifically for families who have been recently diagnosed. Here we have provided tools to manage the first 30 days, identify what parents need to know now, and how they can get support.
• Obtaining Comprehensive Care: PPMD’s network of Certified Duchenne Care Centers are centers that are capable of providing comprehensive Duchenne care in agreement with the Care Considerations (see ‘Caring for Duchenne’, below).  Each of these centers include sub-specialists with Duchenne expertise across the spectrum and lifespan of the disease. These centers exist as a resource to both you and your families. If you need assistance in accessing the CDCC network, a center in your area or have questions/need resources that you are having difficulty accessing, please contact PPMD.

PPMD brought together neuromuscular specialists to review CK testing, including how it supports the diagnosis of dystrophinopathy, reasons CK levels may be elevated in people without dystrophinopathy, how levels can change with age, and what an elevated result can and cannot tell you in clinical practice.

Interpreting CK Levels in the Diagnosis of Duchenne

Video 1 Question Group – An Introduction to Creatine Kinase (CK) Levels

1. What is creatine kinase?
   Creatine kinase, sometimes referred to CK for short, is an enzyme found in many different tissues in our body. The highest amounts are found in our muscles and our heart. An enzyme is something that helps speed up chemical reactions in the body. CK is one of those enzymes, and its main job is to help provide energy to our muscle cells.
2. Why is creatine kinase (CK) elevated for Duchenne and Becker muscular dystrophy?
   A small amount of CK is normally present in our blood, and we can measure it with a simple blood test. When CK levels are higher than normal, it often means the muscles are under stress or have been damaged. In Duchenne and Becker muscular dystrophy, the body lacks a protein called dystrophin, which helps keep muscle cells strong and stable. You can think of the cell membrane as the outer covering of a muscle cell. It controls what goes in and out. Without enough dystrophin, the membrane becomes fragile, and CK can leak out of the muscle cells into the blood, leading to higher CK levels on a test.
3. Is CK elevated for every person with Duchenne or Becker?
   CK is very sensitive for Duchenne and Becker, meaning it’s usually elevated in almost everyone with these conditions. However, it’s not a perfect test. CK levels can be influenced by many factors, including the age at which the test is done. In general, a normal CK level in a young child is quite reassuring and makes Duchenne less likely. Most children with Duchenne will have a high CK level early in childhood.
4. Are there reasons why CK could be elevated in a person without muscular dystrophy?
   There are many reasons a CK level can be elevated. Some common causes include muscle injury or stress, inflammation in the muscles, certain medications, or even severe illness. Strenuous exercise can also raise CK levels. Additionally, there are other muscle disorders, besides Duchenne and Becker, where CK may also be elevated.
5. Do people with Duchenne and Becker have elevated CK every day of their life?
   CK levels can fluctuate somewhat over time, both in the short term and long term. In people with Duchenne, CK levels are usually highest in early childhood and then gradually decrease as a person gets older. This drop tends to follow the loss of motor function. As muscles weaken, there is less healthy muscle tissue, and over time that muscle is replaced by fat and scar tissue. Because of this, there’s less CK released into the blood, which is why CK levels tend to go down with age.
6. Sometimes test reports will reference things like CPK, CK-MM, or CK total – what is important for families to understand about the differences between these? Are they different from each other?
   CPK stands for creatine phosphokinase, and it’s essentially the same thing as CK, or creatine kinase. The terms are used interchangeably, though CPK refers a bit more specifically to the chemical reaction the enzyme helps with. CK actually exists in a few different forms, sometimes called isoforms. Different tissues in the body make different amounts of each form. For example, CK-MM is mostly found in skeletal muscle, CK-MB is found in the heart, and CK-BB is found in the brain. When we measure a total CK, that number represents the sum of all these isoforms. If any one of them is elevated, it contributes to a higher total CK. Looking at which isoform is elevated can help determine where the CK is coming from, whether it’s the muscles, the heart, or the brain.

Video 2 Question Group: Interpreting CK Levels in the Clinic

1. How do you use CK level results in your clinic?
   CK levels are really a first step in looking for any signs of muscle breakdown in a patient. At an initial clinic visit, if there are signs of muscle weakness or developmental delays, it’s common to order a CK test. The results can point to a number of possible conditions related to muscle damage. It’s a simple, inexpensive screening tool that can be done easily in most clinics.
2. If a person has an elevated CK result, is there a threshold for which you can tell if they will be affected by Duchenne versus Becker muscular dystrophy?
   CK levels can help point us in the direction of a possible muscular dystrophy, but other tests are needed to make a specific diagnosis. Think of CK as a screening tool. It can raise suspicion for Duchenne, Becker, or other types of muscular dystrophy, but additional testing, usually genetic, is needed to confirm what is going on. A normal CK level also does not rule out a muscle disorder completely. Some congenital myopathies or other muscle conditions can have normal CK levels. Most muscular dystrophies, however, will show an elevated CK. So it is a helpful first step in the diagnostic process, but it is just the starting point.
3. Can a child with multiple normal CK levels go on to develop Duchenne muscular dystrophy in the future? What about Becker muscular dystrophy?
   It would be very unusual for a child with multiple normal CK levels to develop Duchenne in the future. While CK is not very specific for the type of muscular dystrophy, it is usually very high in patients who do have muscular dystrophy. Patients who have had normal CK levels, especially on multiple occasions, are very unlikely to develop muscular dystrophy in the future.
4. Will carriers have high CK levels? Can a CK level confirm if someone is a carrier or not?
   CK is not a reliable way to determine who is a carrier of a DMD gene mutation. Some female carriers may have mildly elevated CK levels, but many carriers have normal CK levels, so a normal result does not rule out carrier status. In cases where a female with a known DMD mutation has a high CK level, it could suggest she is a manifesting carrier, and specialists may pay closer attention to potential symptoms. However, CK alone cannot determine the presence of heart or other symptoms in carriers. Identifying subtle symptoms in carriers requires a detailed evaluation by a specialist, not just a CK test.
5. If a person has a genetic test report that says they have an abnormal DMD gene, due to a pathogenic variant, and their CK is normal, does that eliminate the possibility that they will develop symptoms in the future?
   If a person has a normal CK and a genetic test identifying a variant, it generally rules out Duchenne or Becker muscular dystrophy, especially if CK has been normal on multiple occasions. Some variants in the DMD gene may be benign, so interpreting the results usually requires guidance from a neuromuscular specialist or a genetic counselor familiar with the DMD gene.
6. What advice do you have for someone who has a CK result they don’t understand?
   The best approach is to ask your doctor to help interpret the results. If your primary care doctor ordered the test, start there. They may know the answer or may need to consult a specialist. You can also take the question directly to a neuromuscular specialist. CK levels can be tricky to interpret, so getting input from a specialist can be very beneficial.
7. Is there anything else you’d like to make sure patients and healthcare providers know about CK level?
   The most important thing is simply to check CK levels, especially in any child with motor delays. Checking CK early and, if needed, checking it regularly can help identify muscular dystrophy sooner. A very high CK does not automatically predict what will happen in the future. High CK can have many causes, and even when it reflects muscular dystrophy, outcomes are not set in stone. Advances in care and new treatments continue to change what is possible, so the future remains uncertain. The key is early evaluation and monitoring, not assuming results dictate the long-term course.

Video 3 Question Group: CK Levels and Newborn Screening

1. Why is CK level the measurement that will be used for Newborn screening for Duchenne?
   There are a few important considerations when choosing a marker for newborn screening. Newborn screening is done using a dried blood spot, which involves taking a small amount of blood from a baby’s heel and placing it on a card that is sent to the state screening lab. The marker needs to be stable and accurate in this dried form and also feasible to test on a very large scale, since nearly all babies in the United States undergo newborn screening. The marker should also reliably identify babies who are affected while excluding those who are not. Even though babies with Duchenne do not show symptoms at birth, their CK is elevated, making it a very effective marker for detecting the condition through newborn screening.
2. What could cause a false positive newborn screen for Duchenne?
   There are several reasons a newborn screen for Duchenne might be false positive, mainly because the test uses CK rather than genetic testing. While CK is very sensitive for Duchenne, it is not 100% specific. Common causes of false positives include birth trauma, infection during the neonatal period, and other muscle disorders. CK levels are also naturally higher during the first 24 to 48 hours after birth, since the physical process of birth, even a C-section, can be demanding for newborns. The timing of the screen and whether it is repeated can help determine whether an elevated result is more or less likely to be a false positive.
3. Do we think NBS will detect 100% of people with Duchenne? If not, what could lead to a false negative?
   Ideally, the goal of newborn screening is to detect every case of Duchenne. However, no screening test is perfect. There can be variability in lab cutoffs, which determine how high CK must be to trigger a positive screen. Some factors can elevate CK, while others can lower it. Prematurity and very low birth weight are known examples. If the CK measurement falls below the cutoff, it is possible the baby could be missed by newborn screening. This is uncommon, but it has been observed in previous pilot programs. Finally, while very rare, there is always a small risk of technical or human error.
4. Will newborn screening detect people with Becker muscular dystrophy or people who are carriers?
   Unfortunately, the answer here is not straightforward. For both people with Becker muscular dystrophy and DMD carriers, CK elevation at birth is more variable than in Duchenne. However, pilot studies and newborn screening programs that have been implemented so far have successfully detected both.
5. What should someone do if they get a call about a positive CK screen for Duchenne on newborn screening?
   First and foremost, it’s important to try to remain calm. CK is a screening test and by itself is not diagnostic. The evaluation pathway can vary depending on your state. It might involve repeating the test, since CK is typically highest in the first few days of life when the newborn screen is usually done and often normalizes afterward. Alternatively, the next step could be a referral to a genetic or neuromuscular specialist. For parents or family members, it is important to be selective about the resources you use for information. For healthcare providers, it’s recommended to review your state’s screening protocol and discuss next steps with neuromuscular colleagues.
6. Is there anything else you’d like to make sure patients and healthcare providers know about CK level?
   It’s important to remember that newborn screening programs are state-dependent. You can’t assume your state screens for Duchenne just because other states do. Even if your state does include Duchenne in its newborn screening, any child presenting with developmental delays should still have a CK test. CK is a valuable screening tool both in the newborn period and later in life, so it should always be considered when evaluating a child with developmental delays.