Retrospective analysis supports algorithm as efficient diagnostic approach to treatable intellectual developmental disabilities

Bryan Sayson; Marioara Angela Moisa Popurs; Mirafe Lafek; Ruth Berkow; Sylvia Stockler-Ipsiroglu; Clara D M van Karnebeek

doi:10.1016/j.ymgme.2015.03.001

Retrospective analysis supports algorithm as efficient diagnostic approach to treatable intellectual developmental disabilities

Mol Genet Metab. 2015 May;115(1):1-9. doi: 10.1016/j.ymgme.2015.03.001. Epub 2015 Mar 9.

Authors

Bryan Sayson¹, Marioara Angela Moisa Popurs², Mirafe Lafek², Ruth Berkow³, Sylvia Stockler-Ipsiroglu⁴, Clara D M van Karnebeek⁵

Affiliations

¹ Division of Pediatric Neurology, BC Children's Hospital, Vancouver, Canada; Department of Pediatrics, BC Children's Hospital, Vancouver, Canada; Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, Canada; University of British Columbia, Vancouver, Canada.
² Department of Pediatrics, BC Children's Hospital, Vancouver, Canada; Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, Canada; Division of Biochemical Diseases, BC Children's Hospital, Vancouver, Canada.
³ Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, Canada.
⁴ Department of Pediatrics, BC Children's Hospital, Vancouver, Canada; Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, Canada; Division of Biochemical Diseases, BC Children's Hospital, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada; University of British Columbia, Vancouver, Canada.
⁵ Department of Pediatrics, BC Children's Hospital, Vancouver, Canada; Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, Canada; Division of Biochemical Diseases, BC Children's Hospital, Vancouver, Canada; Child and Family Research Institute, Vancouver, Canada; University of British Columbia, Vancouver, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada. Electronic address: cvankarnebeek@cw.bc.ca.

PMID: 25801009
DOI: 10.1016/j.ymgme.2015.03.001

Abstract

Background: Intellectual developmental disorders (IDD(1)), characterized by a significant impairment in cognitive function and behavior, affect 2.5% of the population and are associated with considerable morbidity and healthcare costs. Inborn errors of metabolism (IEM) currently constitute the largest group of genetic defects presenting with IDD, which are amenable to causal therapy. Recently, we created an evidence-based 2-tiered diagnostic protocol (TIDE protocol); the first tier is a 'screening step' applied in all patients, comprising routinely performed, wide available metabolic tests in blood and urine, while second-tier tests are more specific and based on the patient's phenotype. The protocol is supported by an app (www.treatable-ID.org).

Objective: To retrospectively examine the cost- and time-effectiveness of the TIDE protocol in patients identified with a treatable IEM at the British Columbia Children's Hospital.

Methods: We searched the database for all IDD patients diagnosed with a treatable IEM, during the period 2000-2009 in our academic institution. Data regarding the patient's clinical phenotype, IEM, diagnostic tests and interval were collected. Total costs and time intervals associated with all testing and physician consultations actually performed were calculated and compared to the model of the TIDE protocol.

Results: Thirty-one patients (16 males) were diagnosed with treatable IDD during the period 2000-2009. For those identifiable via the 1st tier (n=20), the average cost savings would have been $311.17 CAD, and for those diagnosed via a second-tier test (n=11) $340.14 CAD. Significant diagnostic delay (mean 9 months; range 1-29 months) could have been avoided in 9 patients with first-tier diagnoses, had the TIDE protocol been used. For those with second-tier treatable IDD, diagnoses could have been more rapidly achieved with the use of the Treatable IDD app allowing for specific searches based on signs and symptoms.

Conclusion: The TIDE protocol for treatable forms of IDD appears effective reducing diagnostic delay and unnecessary costs. Larger prospective studies, currently underway, are needed to prove that standard screening for treatable conditions in patients with IDD is time- and cost-effective, and most importantly will preserve brain function by timely diagnosis enabling initiation of causal therapy.

Keywords: Cost-effectiveness; Diagnosis; Global developmental delay; Inborn errors of metabolism; Intellectual disability; Treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Algorithms*
British Columbia
Child
Cost-Benefit Analysis
Delayed Diagnosis
Diagnosis, Computer-Assisted* / economics
Diagnosis, Computer-Assisted* / methods
Humans
Intellectual Disability / diagnosis*
Male
Metabolism, Inborn Errors / complications*
Metabolism, Inborn Errors / diagnosis
Morbidity
Phenotype
Retrospective Studies
Time Factors