An Exploration of Genetic Test Utilization, Genetic Counseling, and Consanguinity within the Inborn Errors of Metabolism Collaborative (IBEMC)

Abstract

The Inborn Errors of Metabolism Collaborative (IBEMC) includes clinicians from 29 institutions collecting data to enhance understanding of metabolic conditions diagnosable by newborn screening. Data collected includes hospitalizations, test results, services, and long-term outcomes. Through evaluation of this data, we sought to determine how frequently genetic counseling had been provided, how often genetic testing was performed, and also determine the consanguinity rate in this population. A data query was performed with the following elements abstracted/analyzed: current age, metabolic condition, whether genetic counseling was provided (and by whom), whether genetic testing was performed, and consanguinity. Genetic counseling was provided to families 95.8% of the time and in 68.6% of cases by a genetic counselor. Genetic testing was performed on 68.0% of subjects, with usage highest for fatty-acid-oxidation disorders (85.1%). The rate of consanguinity was 2.38%. Within this large national collaborative there is a high frequency of genetic counseling, though in one-third of cases a genetic counselor has not been involved. Additionally, while metabolic conditions have historically been diagnosed biochemically, there is currently high utilization of molecular testing suggesting DNA testing is being incorporated into diagnostic assessments - especially for fatty-acid-oxidation disorders where the underlying genotype helps predict clinical presentation.

Genetic testing experiences and genetics knowledge among families with inherited metabolic diseases

“…Additional research also is needed to understand factors that impact clinicians' decisions to offer genetic testing for IMDs and whether benefits outside of clinical utility are considered (e.g., knowledge, cascade testing of family). It also is not known how many families with IMDs have been counseled about the potential benefits and risks of genetic testing, although a study by Stein and colleagues found that genetic counseling rates were high among families with IMDs [ 8 ]. While our study focused on families with IMDs, expanded carrier screening programs that include genes for IMDs leads to the identification of additional families in need of genetics education.…”

“…Identification of pathogenic genetic variants can also impact the broader family [ [4] , [5] , [6] ], including the feasibility of carrier testing [ 7 ]. Despite these recommendations, only approximately two-thirds of individuals with an IMD report having received genetic testing with testing rates varying across condition, ranging from 34% to 100% [ 8 ]. Genetic testing should be accompanied by genetic counseling to ensure appropriate informed consent prior to testing, comprehension of test results, and understanding of implications for medical care and genetic risk of other family members [ [9] , [10] , [11] ].…”