Infant DNA Tests Speed Diagnosis of Rare Diseases

I just read an article in the Health section of the New York Times that was interesting.  The whole article can be read by following the link above, but I have pasted a couple of sections below for your reading.

I believe the most interesting comment was, “… families greatly valued the diagnosis.”  Knowing if often far better than not knowing.  Or, as I have often said, “the best surprise is not surprise at all.”

I can understand the value of this type of testing over the older, more established methods of trial and error, … testing based upon symptoms that show up.

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…. The idea behind the test is to take advantage of what is known about disease symptoms to narrow the search for genetic aberrations. And that, said Dr. Joe Gray, an expert in genome analysis at Orego
 
“It’s a big genome,” said Dr. Gray, who was not involved with the study. “How do you know what part of it to search?” 
 
While more research needs to be done before the test is ready for widespread use, he applauded the effort. “If people don’t push the envelope like this, then we won’t get there,” Dr. Gray said. 
 
About one in 20 babies in newborn intensive care units has a genetic disease, and all too often, no one can figure out what it is. Scientists identified the faulty genes for about 3,500 of 7,500 known genetic diseases, said the paper’s authors, adding that about 500 have treatments.

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… With the new method, a computer program searches for genes based on the baby’s symptoms. And because it focuses only on genes that cause diseases in newborns, it avoids an ethical problem: findings that are unrelated to the problem at hand. In sequencing and analyzing the entire DNA, researchers may discover, for example, aberrations leading to conditions that occur only in adults. Do parents really want to know that their sick baby has a gene that increases the risk of Alzheimer’s disease? 
 
“They did it right, and you rarely hear that from an ethicist,” said Dr. Lainie Friedman Ross, an ethicist and professor of pediatrics at the University of Chicago. Dr. Ross, who praised the researchers for deliberately avoiding such incidental findings, was also not involved with the study.
The method is expensive, though, costing about $13,500. It is not yet covered by insurance. 
 
But Dr. Stephen F. Kingsmore, director of Children’s Mercy’s center for pediatric genomic medicine, expects to show it is cost effective and hopes insurers will pay for it. He noted that each day a baby spends in intensive care costs about $8,000, so any test that reduces that time would quickly pay for itself. A test that reveals a uniformly fatal genetic disease, for example, can allow parents and doctors to know that continuing life support in the hope the baby will improve is futile and only causing suffering. In the meantime, Dr. Kingsmore said, he is hoping a philanthropist will help defray the costs.

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… The biggest surprise for Dr. Kingsmore, though, was that the families greatly valued having a diagnosis. 
 
When a baby has a mysterious disease, he said, the family often embarks on a terrifying diagnostic odyssey. “Test after test is performed,” he said. “Some tests are invasive; the child is suffering. The child is getting worse and worse — most spend their entire lives in the hospital, and there is no answer.” 
 
Just knowing the answer can be a comfort. “Providing a definitive diagnosis somehow brings closure,” Dr. Kingsmore said. “It is something they can name.”

Genetics Test for ALS now available

The Summer MDA Newsletter had the following article:

“The Athena Diagnostics Division of Quest Diagnostics announced that on April 30, 2012 the first clinically available testing service designed to detect the C9ORF72 repeat expansion mutation that can cause both ALS and frontotemporal dementia (FTD). The C9ORF72 mutation was identified in September 2011 and appears to be the most common known cause of familial ALS, FTD and ALS with FTD. The mutation underlies approximately 40% of familial ALS cases, and also has been found to be responsible for about 8% of sporadic ALS. (Familial ALS refers to situations in which there is more than one known occurrence of ALS in the family; sporadic ALS refers to situations in which there is no known occurrence of the disease in other family members.)


The new genetic test is offered to help speed the diagnosis of ALS. It will be available to clinicians as a standalone test or as part of multigene testing. For testing locations, visit the National Center for Biotechnology Information’s Genetic Testing Registry at http://ncbi.nih.gov/gtr/tests/?term=C1862937.


Those considering genetic testing should speak with their physician. Consultation with a genetic counselor, who can help obtain and interpret the results of genetic testing, is recommended.”


You might ask why this announcement is important to those of us living with Kennedy’s Disease. The most common misdiagnosis for for the mutated CAG triplets repeat gene is ALS. I was one of the people initially misdiagnosed and I know dozens of others that also were misdiagnosed with familial ALS. The initial misdiagnosis of ALS has shattered many lives causing unnecessary stress and often life changing decisions. Having a DNA test that covers approximately 48% of the occurrences of ALS will help rule out that particular disorder when the doctor is unaware of Kennedy’s Disease.

What does the DNA blood test tell us?

At least a couple of times a year someone will write and question the accuracy of the DNA blood test for Kennedy’s Disease. This normally happens because a man has identified many of the symptoms he has are also related to Kennedy’s Disease (KD).

It is my understanding that the DNA test is 99+% accurate. Yes, that still leaves less than one percent available for error. Of course, there is the possibility that a person is ‘borderline’ KD. That means his CAG repeats are 34-39. It is also my understanding that borderline cases can exhibit some of the symptoms, but not all of them. The progression is also not as evident.

The two DNA tests that I had showed a scale similar to the following:

• 0-33 = Normal
• 34-39 = Borderline
• 40 and above = Kennedy’s Disease (Spinal Bulbar Muscular Atrophy or SBMA)

So, borderline could be diagnosed as normal by some doctors and also explain why a patient experiences some of the symptoms.

In a study conducted a few years ago, it was reported that the higher the CAG repeat count the earlier the onset meaning the progression is also more apparent over time. I happen to be on the higher end with a 53. I have known others with counts in the low 40s that did not exhibit any noticeable symptoms until the late 50s or 60s. (Boy would that have been nice)

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Wikipedia defines these type disorders as Trinucleotide repeat disorders (also known as trinucleotide repeat expansion disorders, triplet repeat expansion disorders or codon reiteration disorders) are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in certain genes exceeding the normal, stable, threshold, which differs per gene. The mutation is a subset of unstable microsatellite repeats that occur throughout all genomic sequences. If the repeat is present in a healthy gene, adynamic mutation may increase the repeat count and result in a defective gene.


Wikipedia also explains Kennedy’s Disease as: SBMA is caused by expansion of a CAG repeat in the first exon of the androgen receptor gene (trinucleotide repeats). The CAG repeat encodes a polyglutamine tract in the androgen receptor protein. The greater the expansion of the CAG repeat, the earlier the disease onset and more severe the disease manifestations.