small microscope

Rare Disease Laboratory Testing - all things are not equal

After spending exorbitant sums of money sometimes measured in the thousands, many families discover that testing obtained through alternative mechanisms is not considered “diagnostic” data for most physicians. Due to roadblocks placed by or knowledge deficits in the medical community many sidelined patients pursue answers independently in hopes of findings treatments and cures for themselves or loved ones.  Upon discovering their “answers” are not considered legitimate information for diagnosis many families will ask, “What parameters are utilized to define legitimate and recognized testing?”

In the past, complicated rare disease testing, which is often very expensive and sometimes invasive, was available only through referral by medical providers.   However, advances in medical science have resulted in the availability of a variety of studies utilizing simple blood and now saliva samples making it widely accessible to the public at large. This has led many patients and families to independently pursue testing through various laboratories that offer data interpretation and recommendations for management of abnormal findings.  With advances in genomic testing, molecular studies offered by a variety of entities have also entered into this arena of available testing for a fee.

Congress passed the Clinical Laboratory Improvement Amendments (CLIA) in 1988 establishing quality standards for laboratory testing to ensure accuracy, reliability, and timeliness of patient test results regardless of where the test was performed.  A laboratory is defined as any facility which performs laboratory testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention, treatment of disease, or impairment or assessment of health. 

Qualified laboratories performing human testing are therefore required to maintain CAP (College of pathology) and CLIA (Clinical Laboratory Improvement Amendments) certification. Additionally, insurance reimbursement for laboratory services dictates maintenance of CAP and CLIA certification. To maintain the certifications, laboratories must pass unannounced inspections by state regulators and accurately assess unknown samples proving competency in the testing provided (proficiency testing). Failure to do so results in loss of certification, inability of the laboratory to continue performing patient testing, and loss of insurance contracts.

As such, using a Lab that is not CLIA certified means that no one is held accountable to quality standards and reliability testing, and that insurance will not reimburse for testing performed. Therefore, as a parent or patient, one should ensure that the testing laboratory you have selected or are being referred to for studies has and maintains certification for quality assurance purposes.

Unfortunately, though, maintaining CAP and CLIA certification alone does not ensure that one will receive accurately INTERPRETED data. For example, while some laboratories that run amino acid samples may provide accurate numbers and levels of various amino acids, their interpretation of the data may be questionable. So, for instance, some laboratories recommend introduction of various supplements based on testing results although they fail to inform the patient that the same amino acid profile collected at different times during the same day or before or after a meal can result in very different profiles. As such, mild variations in amino acids are not reflective of a disease process and may not even be reflective of a deficiency meaning that no treatment should be implemented for nonspecific variations identified on an isolated profile. If concerns persist for possible diagnoses or deficiencies, the testing should be repeated and the abnormalities should be documented on more than one study before an identified abnormality should be considered to be a true problem.

Similar limitations may exist in the interpretation of molecular data. We utilize certain CAP and CLIA certified laboratories in the evaluation of our patient population because of their extensive experience in advanced genomic studies and their ability to interpret the data and utilize databases for accurate diagnostic purposes.

In addition, in regards to genomics, a number of labs have arisen that market gene testing directly to the public. While the data generated may be interesting or fascinating from a family genealogic perspective or other broad spectrum issues, it is not useful in the definitive diagnosis of specific genetic disorders and often creates confusion and concern identifying a variety of genetic changes that may be polymorphisms or benign genetic alterations that are misinterpreted by the patient as reflective of a disease or disease process.  Remember that no one has perfect genes, so variants will ALWAYS be uncovered with this testing.  However, this testing is not helpful in the diagnosis of specific genetic disorders and, as such, should not be utilized for that purpose. Geneticists like myself will not utilize and cannot utilize it for the diagnosis of specific genetic disorders and must rely on qualified reference labs for that purpose.

In summation, laboratory data is a mainstay of modern medical science. However, patients and families should be mindful of completing laboratory studies in unregulated laboratories and should confirm abnormalities on a given test by repeating the study if at all possible before implementing treatment.  In addition, caution must be taken when utilizing broad-spectrum genomic studies as they are not helpful for the specific diagnosis of a given genetic or metabolic disorder. Ideally, it is best to seek the advice of a trusted medical professional to help navigate the quagmire of testing and to prevent needless expenses for studies that ultimately prove useless for you or your child's diagnosis and management. Otherwise, you may find that you have spent thousands of dollars on testing that no one will even consider in their evaluation of you or your child's problems.


Fran Kendall, M.D.

This post is not meant to be a recommendation or a substitute for professional advice and services rendered by qualified doctors, allied medical personnel, and other professional services. The responsibility for any use of this information, or for proper medical treatment, rests with you.