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

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

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

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).

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.