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

Abstract

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. To determine whether patients with genetically confirmed mitochondrial disease are shorter than their peers and whether stature is related to disease severity. Analysis of final adult height in relation to disease severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS). UK Mitochondrial Disease Patient Cohort (Mito Cohort). 575 patients were identified with recorded height, weight, and molecular genetic diagnosis of mitochondrial disease within the Mito Cohort. Adult height, body mass index (BMI), and their association with genetic subgroup and disease severity. 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). Final height in mitochondrial disease reflects disease severity and rate of disease progression. Mitochondrial dysfunction and associated subclinical comorbidities affect growth plate physiology.