The evolution of the mitochondrial disease diagnostic odyssey

Abstract

Background: Mitochondrial diseases often require multiple years and clinicians to diagnose. We lack knowledge of the stages of this diagnostic odyssey, and factors that affect it. Our goals are to report the results of the 2018 Odyssey2 (OD2) survey of patients with a medical diagnosis of mitochondrial disease; and to propose steps to reduce the odyssey going forward, and procedures to evaluate them.

Methods: Data are from the NIH-funded NAMDC-RDCRN-UMDF OD2 survey (N = 215). The main outcomes are Time from symptom Onset to mitochondrial disease Diagnosis (TOD) and Number of Doctors Seen during this diagnostic process (NDOCS).

Results: Expert recoding increased analyzable responses by 34% for final mitochondrial diagnosis and 39% for prior non-mitochondrial diagnosis. Only one of 122 patients who initially saw a primary care physician (PCP) received a mitochondrial diagnosis, compared to 26 of 86 (30%) who initially saw a specialist (p < 0.001). Mean TOD overall was 9.9 ± 13.0 years, and mean NDOCS 6.7 ± 5.2. Mitochondrial diagnosis brings extensive benefits through treatment changes and increased membership in and support of advocacy groups.

Conclusions: Because TOD is long and NDOCS high, there is great potential for shortening the mitochondrial odyssey. Although prompt patient contact with primary mitochondrial disease specialists, or early implementation of appropriate tests, may shorten the diagnostic odyssey, specific proposals for improvement require testing and confirmation with adequately complete, unbiased data across all its stages, and appropriate methods. Electronic Health Record (EHRs) may help by accessing diagnostic codes early, but their reliability and diagnostic utility have not been established for this group of diseases.

Fig. 1

A Self-reported mitochondrial disease diagnoses before and after expert recoding of text responses. Each patient provides 1 response. N = 215. POLG, Polymerase gamma related disorders/ataxia neuropathy spectrum; KSS, Kearns–Sayre syndrome; LHON, Leber hereditary optic neuropathy; MERRF, Myoclonic epilepsy with ragged-red fibers; PDC, Pyruvate dehydrogenase complex; NARP, Neuropathy, ataxia, and retinitis pigmentosa. B Self-reported prior non-mitochondrial disease diagnoses before and after expert recoding of text responses each patient can provide more than one response. "Other" responses could be recoded into several existing or new responses. N = 259 responses after recoding, 246 responses before

Fig. 2

A Age at first symptom(s) of mitochondrial disease (N = 209); B Age at diagnosis of mitochondrial disease (N = 198); C Time from first symptoms to diagnosis of mitochondrial disease (N = 198)

Fig. 3

Evolution of mitochondrial disease diagnosis by specialty of diagnosing clinician. At each node (First Doctor Seen; Specialty; Did they give a mito diagnosis?; Final doctor’s specialty; and Final Doctor a Mito Expert?), Ns (%s) sum vertically. (N = 215 patients)