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Endocrine Abnormalities and Growth Pattern in Single Large-Scale Mitochondrial DNA Deletion Syndromes
Ayman Daka1,2, Einat Lahav2,3, Omer Bar Yosef2,4
1Pediatric Ward, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Israel.
Insights
Children with single large-scale mitochondrial DNA deletion syndromes (SLSMDs) frequently develop endocrine disorders, including short stature and hypoparathyroidism. Growth is significantly impaired during childhood and adolescence in SLSMD patients.
Area of Science:
- Genetics and Endocrinology
- Mitochondrial Diseases
- Pediatric Growth and Development
Background:
- Single large-scale mitochondrial DNA deletion syndromes (SLSMDs) are rare genetic disorders.
- Endocrine dysfunction and growth abnormalities are suspected but not well-characterized in SLSMD patients.
Purpose of the Study:
- To determine the prevalence of endocrine disorders in children with SLSMDs.
- To analyze growth patterns and identify specific growth deficits in this population.
Main Methods:
- Retrospective analysis of 18 children diagnosed with SLSMD at Sheba Medical Center between February 2017 and September 2024.
- Collection and analysis of endocrine disorder diagnoses, height measurements, and growth standard deviation scores (SDS).
Main Results:
- All patients (100%) developed at least one endocrine disorder within five years of diagnosis.
- The most common endocrine issues were short stature (94%), hypoparathyroidism (83%), diabetes (33%), and delayed puberty (30%).
- Growth during childhood and adolescence was significantly reduced compared to the general population, with lower height-SDS and insulin-like growth factor 1-SDS.
Conclusions:
- Endocrine disorders are a universal complication of SLSMDs.
- SLSMD patients exhibit significantly impaired growth trajectories.
- Routine and timely endocrine evaluations are crucial for managing patients with SLSMDs.
Aim:
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).
Conclusion:
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.
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