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

• Published in: The journal of clinical endocrinology and metabolism 2019-06, Vol.104 (6), p.2057-2066
• Main Authors: Boal, Rachel L, Ng, Yi Shiau, Pickett, Sarah J, Schaefer, Andrew M, Feeney, Catherine, Bright, Alexandra, Taylor, Robert W, Turnbull, Doug M, Gorman, Grainne S, Cheetham, Tim, McFarland, Robert
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adults; Aged; Aged, 80 and over; Body height; Body Height - genetics; Body Mass Index; Body weight; Clinical s; Disease Progression; Female; Genetic screening; Growth Disorders - diagnosis; Growth Disorders - genetics; Growth plate; Humans; Male; Middle Aged; Mitochondria; Mitochondrial Diseases - complications; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - genetics; Overweight; Physiological aspects; Retrospective Studies; Severity of Illness Index; United Kingdom; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-00957

Abstract 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. Patients with mitochondrial disease are shorter than the general population, with adult height related to disease severity and rate of disease progression.