‘Diagnostic hell” was the way that Mary Jo Reich, a mother of two from Short Hills, N.J., described her son Scott’s battery of misdiagnoses. Although pediatricians had told Reich that Scott was following a normal developmental curve for the first eight months of his life, she had always sensed a problem. “He was less than an hour old, and I felt something was wrong in his eyes,” she said. “He wasn’t here.” When Scott was 1 and did not walk, hardly spoke and continued to have low muscle tone, the Reichs were told that he had cerebral palsy. It was not until Scott was 21 months old, after the Reichs had traveled up and down the East Coast in search of a second opinion, that Scott had a conjunctival biopsy, a procedure used to count the eye’s abnormal storage bodies. After the procedure, Scott received a confirmed diagnosis for the first time: Mucolipidosis Type 4, commonly known as “ML4.”
Because cerebral palsy and ML4 share similar symptoms — loss of speech, inability to crawl and walk, mental difficulties — ML4 is frequently misdiagnosed as cerebral palsy. Unlike cerebral palsy, however, ML4 is a rare genetic disease, for which usually 1 in 100 Ashkenazic Jews is a carrier. ML4’s distinguishing feature is corneal clouding, a disorder of the eye that often develops relatively late or is overlooked by physicians making cerebral palsy diagnoses. Given the small number of confirmed ML4 sufferers — diagnosed cases are estimated at about 100 — physicians commonly miss the disease, even though an ML4 gene has been identified and a screening test is available.
According to ML4 Foundation President Randy Yudenfriend Glaser, part of the problem is that the screening test for the disease is not widely used. “The American College of Obstetricians and Gynecologists panel only has four Jewish genetic diseases,” he said, “and ML4 isn’t one of them.” Reich, one of the parents who convinced the National Insitutes of Health to undertake the research that resulted in discovery of the ML4 screening test, said that her goal is not lofty: She simply wants to see a carrier test widely utilized so that her “daughter won’t be an ML4 mother and other families won’t go through” what she has.
To NIH researcher Raphael Schiffmann, frequent misdiagnoses and the lack of testing are frightening from a prevention standpoint. Cerebral palsy isn’t a genetic disorder, but “if you carry ML4, you have a 25% risk with every baby,” he said. It is important for people to know whether they are carriers and if their other children are carriers. Some ML4 carrier couples have gone on to have other children without screening, because their ML4 child had been misdiagnosed with a nongenetic disorder.
While ML4 researchers have made tremendous strides in recent years, there has been a lack of progress on the clinical end. “If we had a larger number of patients, it would be easier to study ML4,” Schiffmann said. Because of the many misdiagnoses, researchers believe there are ML4 patients out there whose families are not aware that they have the disease.
To Reich, what is most disturbing about the cerebral palsy misdiagnosis is that the “ML4 look” — drooping cheeks, low muscle tone, developmental delay and, at times, corneal clouding — is so clear that a 5-year-old can identify it. Reich recalled the story of her daughter’s kindergarten friend, Arielle, asking her if Scott was handicapped. When Reich asked Arielle why she thought so, the girl responded that she has a friend who looks just like Scott. Sure enough, when Arielle’s mother came to pick her up that afternoon, the woman told Reich that her friend’s son did look very similar to Scott, but her friend had been having a very hard time getting a diagnosis. Sure enough, it was ML4.
This story "Similarities Between Cerebral Palsy and ML4 Make Diagnosis a Challenge" was written by Alexa Bryn.