Endocrine Abnormalities and Growth Pattern in Single Large-Scale Mitochondrial DNA Deletion Syndromes.

Objective: To assess the prevalence of endocrine disorders and investigate growth patterns in single large-scale mitochondrial DNA deletion syndromes (SLSMDs).

Methods: A retrospective study of all children with SLSMD who attended Sheba Medical Center, Israel, from February 2017 to September 2024.

Results: The cohort included 18 individuals (9 males). The mean age at diagnosis was 4 ± 3.8 years and the mean age at analysis was 12 ± 5.2 years. All patients exhibited at least one endocrine disorder within 5 years post-diagnosis. The most common were short stature (94%), hypoparathyroidism (83%), diabetes (33%), and delayed puberty (30%). A median of seven height measurements per individual produced 159 data points, which enabled generating unique growth charts. The mean puberty height-SDS was significantly lower than that of the general population (-3.71 ± 1.17, p < 0.001). The mean Childhood and puberty height-SDS were significantly reduced compared to the preschool period (-2.13 ± 1.13 vs. -3.35 ± 1.04, p = 0.01; -2.06 ± 1.03 vs. -3.71 ± 1.17, p = 0.007). The mean delta in height-SDS from their parents and the mean insulin-like growth factor 1-SDS were lower than in the general population (2.36 ± 1.28, p = 0.0001 and - 1.53 ± 0.98, p < 0.0001, respectively).

Conclusions: All patients with SLSMD presented with endocrine disorders. Growth during childhood and adolescence was slower. Patients with SLSMD are predisposed to endocrine complications and should undergo timely and routine evaluations.