Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease

CONTEXT: Abnormal growth and short stature are observed in patients with mitochondrial disease, but it is unclear whether there is a relationship between final adult height and disease severity. OBJECTIVE: To determine whether patients with genetically confirmed mitochondrial disease are shorter than their peers and whether stature is related to disease severity. DESIGN: Analysis of final adult height in relation to disease severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS). SETTING: UK Mitochondrial Disease Patient Cohort (Mito Cohort). PATIENTS: 575 patients were identified with recorded height, weight, and molecular genetic diagnosis of mitochondrial disease within the Mito Cohort. MAIN OUTCOME MEASURES: Adult height, body mass index (BMI), and their association with genetic subgroup and disease severity. RESULTS: Adults with mitochondrial disease were short, with a mean height of -0.49 SD (95% CI, -0.58 to -0.39; n = 575) compared with UK reference data. Patients were overweight, with a BMI SD of 0.52 (95% CI, 0.37 to 0.67; n = 472). The most common genetic subgroup (m.3243A>G mutation) had a height SD of -0.70 (95% CI, -0.85 to -0.54; n = 234) and a BMI SD of 0.12 (95% CI, -0.10 to 0.34; n = 212). NMDAS scores were negatively correlated with height SD (r = -0.25; 95% CI, -0.33 to -0.17; P < 0.001, n = 533). Rate of disease progression also correlated negatively with adult height (P < 0.001). CONCLUSION: Final height in mitochondrial disease reflects disease severity and rate of disease progression. Mitochondrial dysfunction and associated subclinical comorbidities affect growth plate physiology.