Background: Little systematic, large-sample information exists on the characteristics and long-term outcome of children with mitochondrial disorders and cardiomyopathy (CM).

Methods: The NHLBI Pediatric Cardiomyopathy (CM) Registry has collected clinical and long-term outcome data on over 3,500 children meeting strict echocardiographic criteria for CM since 1990. Ninety-nine cases of mitochondrial disease have been indentified.

Results: At time of CM diagnosis, 49% had dilated CM (DCM), 26% had hypertrophic CM (HCM), 22% had mixed/other type of CM (M/OCM), and 2 patients had restrictive CM. Barth syndrome was the etiology in 27%, respiratory chain defects in 17%, and Kearns-Sayre, MELAS, and Senger syndromes in 10%, with the reminder unspecified. In 40%, mitochondrial disease was diagnosed >30 d after CM presentation. Outcome differed by type of CM (p=0.022) with 2-yr mortality being highest in patients with HCM (49%). Two-yr mortality for patients with M/OCM was 36% and with DCM was 17%. Age <1 yr at diagnosis of CM was a significant risk factor for death in patients with HCM.

Conclusions: Approximately 3% of pediatric CM can be attributed to mitochondrial disease, which is likely under diagnosed. Notably, 46% of these patients had unspecified mitochondrial disease and 27% had Barth syndrome. Mitochondrial disorders were associated with all functional types of CM. Patients presenting with HCM, particularly infants, had the poorest survival (51% at 2 years). These first attempts to characterize the patient population may help to better understand the underlying disease pathophysiology leading to earlier and more specific diagnosis.