Needle in a Haystack
Geneticist Gives Family Answer to Elusive Diagnosis
When her son, Markie, was still an infant, Gretchen Noah of Fargo knew something was wrong.
“I have three older children and I know what a child does at what stage,” she says.
The family consulted physicians in Fargo and Rochester, MN.
“We went through many eyes, and they’d say, ‘he’s fine; he’s just tiny,’” she says. People told her and her husband Mark Noah, BSPT ’87, ‘you’ve been to Mayo; let it rest.’”
But Gretchen could not be placated.
“It’s lonely at undiagnosed. It’s frustrating.”
Markie was not correctly diagnosed until John Martsolf, M.D., professor of pediatrics, Grand Forks, recommended the child be tested for Smith-Lemli-Opitz Syndrome (SLOS), a genetic disorder that occurs in one of 40,000-60,000 births and results in the body’s inability to properly metabolize precursors of cholesterol.
In the ten steps the body uses to produce cholesterol, Markie “does the very last step wrong,” Gretchen says, sounding every bit as knowledgeable and well-read as the health professional. Because the body is missing a specific enzyme necessary in the production of cholesterol, the result “is toxic to the brain” and leads to various abnormalities.
“He had a number of the symptoms,” she says. “He had global delays (developmental delays spanning many areas), a heart condition, a pushed-up nose, his thumb and first finger are dwarfed... (yet) he’s one of only 10 percent who does have a regular cholesterol level,” making his a very mild case and therefore difficult to detect.
In the fall 2004, at the age of 11 months, Markie was brought by his family to see Martsolf, North Dakota’s only clinical geneticist, to help unravel the mystery.
Martsolf recommended the family seek a second opinion and requested tests be conducted by laboratory scientists at Mayo, where Markie’s results showed slightly elevated levels of a particular cholesterol precursor that suggests the existence of SLOS.
Markie’s “bloodwork was so mild that they wouldn’t positively” diagnose the syndrome, Gretchen says. The family went further to seek advice from the Kennedy Krieger Institute at Johns Hopkins University School of Medicine in Baltimore where more elaborate, sensitive tests were conducted. Eventually they were invited to the clinic of Forbes Porter, M.D., Ph.D., an internationally recognized specialist in this field at the National Institutes of Health in Bethesda, MD, where the SLOS diagnosis was confirmed.
Markie has “one of the mildest cases (the doctors) have ever seen,” Gretchen says. “Dr. Porter told us it was ‘a great find’ for Dr. Martsolf to have spotted it, and that even he, Dr. Porter, would have had a tough time seeing it.”
Generally, “pediatricians, neurologists and developmental pediatricians tend not to recognize SLOS in the mild form,” Forbes says. “The mild presentations are the hardest to diagnose since they do not have the classical appearance, so this was a very good call by Dr. Martsolf.”
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With Dr. Martsolf’s help, “Now everything’s going great” for Markie, says Markie’s mother, Gretchen Noah of Fargo. |
“Children with SLOS have autistic features, thus understanding the pathophysiological processes that underlie SLOS could provide insight into a more common disorder such as autism,” he explains. “If there is a connection between cholesterol metabolism and autism, understanding the pathophysiological problems in mild cases of SLOS will potentially be very helpful.”
Forbes “was just giddy about Markie,” Mark recalls, because his case “may help drive the treatment for thousands of kids with autism,” the focus of a very large, new initiative. Because symptoms of autism and SLOS are similar, there’s speculation that some children with SLOS may be incorrectly diagnosed as autistic.
Why is it so important to have the correct diagnosis in such cases?
According to Martsolf, “You can’t really talk to the parents about what to expect and about the chances that it would occur again in future children until you have the right diagnosis.”
“As awful as the syndrome is, it’s so much worse to be undiagnosed,” Gretchen says. “We slipped through every crack... It took a geneticist to say, ‘yes, he has the almond eye, he has the pincher grip.’”
“We’re very, very fortunate. When Markie was first diagnosed, he was severely delayed. Now everything’s going great. He runs, he talks, he’s on to four-word sentences – and we expect great things from him.”
“Our son wouldn’t have been diagnosed (with SLOS) without Dr. Martsolf,” Mark says.
“I’m so unbelievably grateful that Dr. Martsolf picked it up,” says Gretchen. “I’m so grateful to him for a number of things he did right.
“I’d love for everybody possible to know that we have an excellent geneticist!”
-Pamela D. Knudson
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