How Is Duchenne Muscular Dystrophy Diagnosed?

Duchenne muscular dystrophy, a condition that affects mostly boys and men, is a genetic disease that causes loss of muscle over time. Currently, testing for the disorder isn’t part of routine screening in newborns. Instead, doctors will test for the condition when they suspect it on the basis ofsymptoms or behaviors characteristic of Duchenne.

The process of diagnosingDuchennetypically involves a series ofblood tests, each one providing key information that determines the next step. One of the first tests that is typically given looks at the breakdown of muscle cells, while a genetic test to find the mutation causing Duchenne tends to be the final diagnostic test.

在极少数情况下,杜乡会的基因测试inconclusive, because not all mutations causing the disease have been firmly identified. If this is the case, your doctor may recommend a muscle biopsy to look for the telltale signs of Duchenne in muscle cells.

When Should a Child Be Tested for Duchenne Muscular Dystrophy?

Since there is no routine screening for Duchenne, the first step in diagnosing the condition is recognizing who needs to be tested. This usually happens when a boy is 3 to 5 years old, and when a parent, caregiver, or doctor recognizes signs of abnormal walking, according toLeigh Maria Ramos-Platt, MD, a pediatric neurologist and the director of the Muscular Dystrophy Association Neuromuscular Clinic at Children’s Hospital in Los Angeles.

But sometimes, it’s only when a child can no longer walk unaided that parents decide to visit a doctor — a situation that Dr. Ramos-Platt sees more often at her hospital than do many of her colleagues at other hospitals in the Los Angeles area.

“我们确实有一个higher proportion of patients who are lower in socioeconomic status and education,” she notes. “Depending on what parents are worried about, it doesn’t dawn on them to see a physician, or they think their kid is going to outgrow it before they come to us.”

Vamshi K. Rao, MD, a pediatric neurologist and the codirector of the Muscular Dystrophy Association Clinic at Lurie Children’s Hospital in Chicago, laments that testing for Duchenne often happens much later than is ideal, “because people have not thought about associated features that you could catch early.”

Dr. Rao notes that there is an established normal range for when young children begin to walk, and that children with Duchenne often start walking at the later end of that range, if not outside it. If a child starts walking later than is typical, this merits investigation for Duchenne, even if the child technically is within the normal range, Rao emphasizes.

“Having said that, the tendency in pediatrics is not to do unnecessary testing, such as blood draws in little children, and rightfully so, most of the time,” says Rao. “But as soon as you think they are trending in that direction” of walking late, when a child is 15 or 16 months old, a doctor should “go ahead and do a simple diagnostic blood test, or refer to a pediatric neurologist or neuromuscular physician.”

Initial Blood Tests for Duchenne Muscular Dystrophy

The most common initial blood test to look for Duchenne — when a child shows early physical signs of the condition — measures an enzyme calledcreatine kinase (CK), which is released into the blood when muscles in the body break down. CK tends to peak in children with Duchenne around age 2 years, when it can be 10 to 20 times the upper limit of what’s considered normal.

If someone without Duchenne had a CK level that high, “it would shut down our kidneys, because we’re not used to it,” Ramos-Platt says. “But if a boy with Duchenne has that number, his kidneys are fine at that point, because his body is used to it.”

不过,有时诊断Duche的过程nne happens not because of physical signs and deliberate testing, but instead when another abnormality is found in routine blood tests.

In some cases, Rao says, routine blood tests find high levels of certainliver enzymes. The muscle also contains these enzymes “and can leak these enzymes into the bloodstream, similar to CK, when it undergoes breakdown,” he explains. “When you see high levels of liver enzymes, it does not always mean that the primary dysfunction is in the liver.”

Some children with undiagnosed Duchenne undergo unnecessary liverbiopsieswhen their liver enzymes are found to be high, an outcome that can easily be avoided, says Rao, by testing for CK. If both are found to be high, doctors can order another test for something calledgamma-glutamyl transferase (GGT). That test, Rao says, “could differentiate between a primary liver problem, when GGT is abnormal, and muscle breakdown” as seen in Duchenne, when GGT is at a normal level.

Genetic Testing for Duchenne Muscular Dystrophy

A physical examination and CK test are usually enough to determine that a child has Duchenne or some other form ofmuscular dystrophy, says Ramos-Platt. “But because a lot of our treatments are very specific to a mutation, I will go ahead with genetic testing” to confirm a diagnosis of Duchenne.

A genetic test for Duchenne looks for an abnormality, or mutation, in the DNA of the gene responsible for the protein dystrophin (called the DMD gene) — causing this protein not to be produced. It typically requires only a standard blood draw, since in someone with Duchenne, this mutation will be present in all cells, not just muscle cells.

A number of different specific mutations on the DMD gene have been identified as causing Duchenne, and genetic analysis will generally focus on the most common mutations first. This means that the technician performing the test will first look for deletions or duplications of long stretches of DNA. If these common mutations aren’t found, they will look for less common mutations on the DMD gene involving small amounts of DNA.

While most mutations on the DMD gene that cause muscular dystrophy are associated with Duchenne, some cause Becker muscular dystrophy, a generally less severe condition in which some functional dystrophin is produced in muscle cells. Genetic testing can almost always identify which form of muscular dystrophy a given mutation causes.

Muscle Biopsy for Diagnosing or Evaluating Duchenne

Before genetic testing became available, the standard way to diagnose Duchenne and other forms of muscular dystrophy was to perform a muscle biopsy. This procedure involves removing a small amount of muscle tissue from an area of the body and looking at it under a microscope.

While a muscle biopsy isn’t a routine part of diagnosing Duchenne anymore, it can still be a useful procedure in some cases.

One situation that may warrant a muscle biopsy is when genetic testing doesn’t make clear whether a child has Duchenne or Becker muscular dystrophy. “In Duchenne you have either a complete lack of dystrophin protein or very tiny amounts, and you can stain for that protein in the muscle,” Rao explains. Pathologists apply special stains to tissue samples to detect the presence of specific protein markers.

In addition, “I will do a muscle biopsy if there is a mutation that predicts Duchenne or Becker, but they don’t seem to be following the pattern,” says Ramos-Platt, who notes that a biopsy can also be useful if a mutation is so rare that it hasn’t been firmly associated with a particular type of muscular dystrophy.

Aside from being used in rare cases to help diagnose Duchenne, muscle biopsies may also be used in clinical trials of Duchenne treatments to look for changes in muscle cells.

Rao estimates that fewer than 10 percent of people get a muscle biopsy as part of diagnosing Duchenne. “Most of the time the genetic diagnosis is pretty revealing,” he says. “And as we publish more, we’re getting better at identifying the correlation between the gene change” and how the disease will affect the child physically and otherwise.

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