Why We Need ICD Codes for Rare Conditions

KRIsten ann ehRenBeRgeR, mD PhD

Her: Did you know there is no ICD-10 code for GRI disorders? Me: Really???

A friend from high school texted me on a Saturday from this year’s GRI Conference in Boston, MA. (Her husband and daughter share a GRIA2 mutation.) We’ve kept in touch regularly since her high-risk pregnancy, through her daughter’s surprise congenital heart defect and surgery at just 7 weeks old, and then the realization that this adorable little girl was not just developmentally delayed but losing milestones. Abby was eventually diagnosed with an uncommon variant of a genetic condition affecting ionotropic glutamate receptors that can cause cortical vision impairment, epilepsy, intellectual disability, Autism, and movement and feeding issues due to hypotonia and motor planning difficulty.

I take care of adults with childhood onset medical complexity, but I had never heard of “GRI Disorders” before my friend’s family was diagnosed. This cluster of mostly missense mutations affects 9 genes for the AMPA receptor (GRIA Disorder), the delta receptor (GRID Disorder), the kainite receptor (GRIK Disorder), and the NMDA receptor (GRIN Disorder). Usually, mutations arise sporadically and de novo, as likely happened with her husband; most cases are due to a single pathological allele with autosomal dominant inheritance. Incidence is currently thought to be as high as 32:100,000 live births for all the known and testable variations (personal correspondence; Lempke 2020). This is many times the incidence of other rare neurodevelopmental conditions such as Rett Syndrome (10:100,000; F84.2) or Dravet Syndrome (6:100,000; G40.834), yet there are no ICD-10 codes for GRI Disorders.

German philosopher Immanuel Kant (1724-1804) is said to have quipped once, “Physicians think they do a lot for a patient when they give his disease a name.” It is true that merely naming a problem does little to relieve a person’s physical suffering. However, it can do a lot to relieve the psychological distress of not knowing what is wrong. The one lesson I still remember from a college professor who is an internist as well as a historian of medicine, Kenneth Ludmerer, is that it is insufficient for the medical team to rule out conditions (malignancy, serious infection, etc.); patients want to know, “What do I have, doc?” The worry may be even greater for parents or caregivers of a child being diagnosed with a lifelimiting condition, as early mortality for neurodevelopmental disorders such as GRI is estimated to be 3x that of the general population, primarily from respiratory infections but also from sudden unexplained death in epilepsy, or SUDEP.

When a collection of subjective symptoms and objective signs can be sorted into a recognizable disease entity, it validates the patient’s complaints. It suggests a pathological why, a therapeutic what, and a prognostic when. In this late-capitalist stage of American health care, in which electronic medical records are designed primarily for billing and secondarily for documentation, a disease name comes with a financial how much. The above numbers for GRI Disorders were derived from calculations of new mutations expected in the population, because we don’t have actual statistics. ICD codes would enable more accurate clinical notes as well as better epidemiological statistics and more clinical trials (there are at least 4 underway right now). Having a name for their child’s condition entitles parents or caregivers to more resources (such as Medicaid waiver funding). Finally, it enables them to locate other families dealing with similar issues, for practical and emotional support.

My friend told me the CureGRIN Foundation has petitioned the Center for Disease Control and Prevention’s National Center for Health Statistics to rectify the lack of specific diagnostic codes, but the conference speaker reported that they were told these conditions are untreatable and therefore don’t need any. That is shortsighted and pessimistic, as there are plenty of (currently) “untreatable”—or better, “uncurable”—conditions with ICD-10 codes (e.g. Alzheimer’s Disease, G30.9). Not to mention the fact that the International Classification of Diseases was born in the 1890s as a standardized list of causes of death and only expanded to include causes of morbidity in 1949. The last time I checked, death is an “untreatable” condition, while the many different therapists who are teaching Abby to stand, drink from a bottle, and use an augmentative and alternative communication device would argue that they are in fact “treating” her.

Now is the perfect time for organizations representing rare but diagnosable conditions to petition for inclusion in the International Statistical Classification of Diseases and Related Health Problems, as the 11th edition was approved by the World Health Organization’s Health Assembly in 2019 and officially went into effect on January 1, 2022. Implementation in the United States has lagged since ICD-8, when the American Hospital Association and US Public Health Service created an adapted version in 1968 (ICDA-8), 3 years after the WHO version, but especially since ICD-9 and 10. Given the expense of updating multiple computer systems for clinical and billing purposes around the country, the US used ICD-9-CM (Clinical Modification) from 1979 through 1998 for mortality, but until 2015 for morbidity. Its successor (ICD10) had been developed in the 1980s, approved by the WHO in 1990, and used throughout the world since 1994.

Clearly it is time for an update. ICD11 is supposed to be adopted here in 2025, or more likely 2027. Hopefully it will include codes that recognize GRIA2 and its sibling conditions.

Sources:

Lemke JR. Predicting incidences of neurodevelopmental disorders. Brain 143:4 (April 2020): 1046-48.

You can read about Abby’s story at curegrin.org/abby. Her mom reports that in the year since her story was published, Abby has learned to sit independently, crawl, and hold her bottle. Explicit permission was received to share these details publicly.