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Published on: September 15, 2017
Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations
Fatma Dursun1, Hulya Maras Genc2, Ayşe Mine Yılmaz3
1Umraniye Training and Research Hospital, Department of Pediatric Endocrinology and Diabetes.
Insights
Biallelic QRSL1 mutations cause combined oxidative phosphorylation deficiency-40 (COXPD40), a condition previously thought to be lethal in infancy. This study reports an 8-year-old patient with non-congenital adrenal hyperplasia primary adrenal insufficiency (non-CAH PAI) due to COXPD40, highlighting the need for adrenal function monitoring.
Area of Science:
- Mitochondrial Biology
- Genetics
- Endocrinology
Background:
- Biallelic QRSL1 mutations lead to combined oxidative phosphorylation deficiency-40 (COXPD40).
- COXPD40 is typically lethal in infancy, with limited prior investigation into adrenal insufficiency.
- Adrenal insufficiency was weakly reported in previous COXPD40 cases.
Observation:
- An 8-year-old boy presented with adrenal insufficiency, developmental delay, hearing loss, cardiomyopathy, nephrocalcinosis, and lactic acidosis.
- Genetic analysis revealed novel biallelic QRSL1 variants.
- The patient exhibited reduced mitochondrial membrane potential and superoxide dismutase activity, indicating mitochondrial oxidative damage.
Findings:
- The patient was diagnosed with non-congenital adrenal hyperplasia primary adrenal insufficiency (non-CAH PAI) and isolated glucocorticoid deficiency.
- This patient represents the longest survival reported for COXPD40 at 8 years.
- Mineralocorticoid functions and gonadal steroidogenesis were preserved throughout the follow-up period.
Implications:
- Biallelic QRSL1 mutations can manifest as non-CAH PAI.
- Monitoring adrenal function is crucial in patients with mitochondrial disorders to improve outcomes.
- This case expands the known clinical spectrum and survival potential of COXPD40.
Background:
Biallelic QRSL1 mutations cause mitochondrial 'combined oxidative phosphorylation deficiency-40' (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40.
Objective:
We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40.
Methods:
The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays.
Results:
An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel QRSL1 variants (c.300T>A;Y100* and c.610G>A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (P < 0.0001). Adrenal function tests revealed a 'primary adrenal insufficiency other than congenital adrenal hyperplasia' (non-CAH PAI) with an isolated glucocorticoid deficiency. In the 8-year follow-up, having the longest survival of reported COXPD40 patients, he had preserved mineralocorticoid functions and gonadal steroidogenesis.
Conclusion:
Biallelic QRSL1 mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.
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