OBJECTIVES: PMM are a group of underdiagnosed rare genetic disorders characterized by a range of clinical presentations and multisystemic impact. Diagnosis and management of PMM can be challenging due to this heterogeneity of clinical manifestations. With no approved treatments for PMM, current practices focus on symptom management and do not address the underlying cause. A patient journey analysis was performed to quantify barriers faced by US patients in their odyssey from clinical manifestation to management.

METHODS: With no PMM-specific ICD-10 diagnosis code, a stepwise approach was needed to identify patients with suspected PMM from Komodo closed-claims data between 2016-2021. This entailed using ICD-10 diagnosis codes specific to mitochondrial disorders (MD) (e.g., chronic progressive external ophthalmoplegia, Kearns-Sayre Syndrome, and Leigh Syndrome), limiting analyses to patients with ≥1 myopathy claim, and excluding those with a secondary MD ICD-10 code.

RESULTS: Of 3.7K patients included for analysis, 97% experienced multi-organ manifestation, impacting an average of 6 organ systems (e.g., nervous, cardiac, musculoskeletal). In the 12 months prior to diagnosis, 73% of patients reported nervous system manifestations and ~70% reported skeletal/muscular manifestations, compared to ~57% and 56% in the 24-36 months prior to diagnosis, respectively. When analyzed by myopathy-related presentations (e.g., impaired gait/mobility, fatigue, myalgia), 36% of patients with suspected PMM had moderate-to-severe presentations, as indicated by inpatient admission or myopathy-related complications (e.g., rhabdomyolysis). Healthcare resource utilization was high, including increased specialist engagement, with most patients seeing a neurologist an average of ~6×/year.

CONCLUSIONS: This patient analysis confirms that PMM encompass a broad spectrum of clinical manifestations and suggests that diagnosis often occurs after multisystem involvement and extensive engagement with the healthcare system. Moreover, it underscores the need for further healthcare provider education about potential manifestations and multiorgan dysfunctions indicative of PMM, along with information to help clinicians make earlier clinical and genetic confirmatory diagnoses for appropriate management.