Mitochondrial disorders are the result of mitochondrial respiratory chain dysfunction and caused by mutations of genes encoded by the nuclear or the mitochondrial DNA. They affect approximately 1 in 5000 of the population and are the most common group of inborn errors of metabolism. Most of them involve multiple organ systems with predominant central nervous system features including ptosis, external ophthalmoplegia and sensorineural hearing loss.
Introduction: Endocrine dysfunction is caused by decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently seen endocrine dysfunction followed by growth hormone deficiency, adrenal dysfunction, hypogonadism and hypoparathyroidism.
Case report: Our patient presented at 3 years of age with vomiting and collapse secondary to tonsillitis. Bloods showed hypoglycaemia, hyponatremia and metabolic acidosis. Cortisol was 239 nmol/l and ACTH was >1500 ng/l. Adrenal antibodies-negative. She was diagnosed with isolated glucocorticoid deficiency and commenced on hydrocortisone. At 8 years of age bloods showed mild hypoparathyroidism. She was also noted to have enamel hypoplasia, slow growth and intermittent diarrhoea. Autoimmune polyglandular syndrome type 1 was considered though there was no mucocutaneous candidiasis. Gene testing for anti IFN alpha IL-17 and 22 and common mutations in AIRE gene were negative. She was diagnosed with bilateral sensorineural hearing loss aged 10. At 11 years of age she was diagnosed with insulin dependent diabetes mellitus. GAD antibodies were strongly positive. Molecular genetic testing in Oxford did not identify any pathogenic variant in AIRE gene. At 16 years of age developed tremors in both hands. CT brain showed hypodensity in both globus pallidi. Mitochondrial disorder was considered as she was noted to have tremors, bradykinesia, rigidity and bilateral ptosis. Her fundal appearance was diagnostic of MIDD (Maternally inherited diabetes and deafness). Genetic testing showed single major mitochondrial DNA rearrangement due to deletion, likely sporadic. Final diagnosis: Mitochondrial disorder and insulin dependent diabetes mellitus.
Learning points: Early consideration of mitochondrial disorders in children presenting with multi organ involvement. Though diabetes mellitus is the common endocrine disorder, primary adrenal insufficiency has been reported prior to the onset of neurological symptoms.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes