ESPE Abstracts

Background: Mitochondrial disorders resulting from single large-scale mitochondrial DNA (mtDNA) deletions (SLSMDs) are a group of non-inherited congenital diseases that lead to three clinically overlapping syndromes: Pearson syndrome (PS), Kearns-Sayre syndrome (KSS), and chronic progressive external ophthalmoplegia (PEO). Although many reports have addressed endocrine abnormalities in patients with SLSMD, there hasn't been an in-depth study on these abnormalities and their specific prevalence.

Objectives: To assess the prevalence of specific endocrine disorders and to investigate the growth pattern among SLSMD patients

Methods: A retrospective analysis was conducted on medical records from individuals at the SLSMD clinic at Sheba Medical Center. Three growth periods were defined: preschool, childhood, and peak-height velocity.

Results: The cohort included 17 individuals (8 males). Mean diagnosis age was 4±3.8 years and mean analysis age was 12.5±4.9 years. All individuals diagnosed with SLSMD exhibited at least one endocrine disorder within the initial 5 years post-diagnosis. The most common among these abnormalities were short stature (94%), hypoparathyroidism (88%), diabetes (30%), and delayed puberty (30%). A median of 8 height measurements per individual, produced 154 data points, which allowed us to generate unique growth charts for children with SLSMD. Mean peak height velocity-SDS was significantly lower compared to the general population (-3.71±1.17, P <0.001). Mean peak height velocity-SDS and childhood height-SDS were significantly lower compared to the preschool period (-2.06±1.03 vs -3.35±1.04, P = 0.004 & -2.06±1.03 vs -3.71±1.17, P = 0.002 respectively). Patients’ mean height-SDS was significantly lower than their parents (∆Height-SDS =2.30±1.3 P <0.0001), and mean IGF1-SDS of the whole cohort was significantly lower compared to the general population (-1.65±0.92, P <0.0001).

Conclusions: The prevalence of endocrine disorders in SLSMD is notable. The finding that all patients with SLSMD experienced at least one endocrine disorder within the initial 5 years post-diagnosis underscores the significance of timely and routine evaluation of endocrine function in those with SLSMD predisposed to endocrine complications. Patients with SLSMD exhibit a distinct growth pattern characterized by a slowdown during childhood and adolescence compared to the general population. We suggest incorporating short stature into the clinical criteria and creating customized growth charts for individuals with SLSMD