Endocrine Abstracts

Introduction: Patients with mitochondrial disease have abnormal cellular adenosine triphosphate (ATP) generation that results in a broad phenotype with a diverse clinical presentation. Abnormal growth and short stature have been observed in children and adults with mitochondrial disease and we hypothesized that stature in affected individuals would reflect disease severity.

Method: We extracted height, weight and molecular genetic data from the UK Mitochondrial Disease Patient Cohort. Height and body mass index (BMI) were compared to the UK reference data. The overall disease severity of individual patients was evaluated using the Newcastle Mitochondrial Disease Scale for Adults (NMDAS), a validated clinical scale to study multi-system involvement and disease progression. We determined the relationship between final height and NMDAS scores in all adult patients by comparing mean height SD for NMDAS bands using a one-way ANOVA; further analysis was conducted in a particular genotype, m.3243A>G mutation, a maternally inherited mutation which is the most common cause of mitochondrial disease.

Results: Adults with mitochondrial disease (n=539) were short with a mean final height of – 0.47 S.D. (CI 95%; −0.57 to −0.38). In 72.2% (n=172) of adults, onset of mitochondrial disease was after the age of 18 years. There was a negative association between height SD and NMDAS score (F (3,535)=9.876, P=<0.00) also observed in the m.3243A>G sub-group (F (3,218)=9.467, P=<0.00). Mean BMI S.D. was 0.53 (CI 95%; 0.529; 0.38–0.68) with no overall association between BMI SD and NMDAS score (F (3,441)=2.347, P=0.072) but a negative association in the m.3243A>G sub-group (F (3,197)=5.957, P=< 0.00).

Conclusions: Short stature in mitochondrial disease is a biomarker of future disease severity as final height is often attained before the onset of overt clinical symptoms. Whilst the etiologies of the short stature are likely multi-factorial, we speculate that abnormal growth plate chondrocyte function secondary to dysfunctional ATP synthesis may be an underlying factor. Further mechanistic studies are warranted.