CASE REPORT Large Mitochondrial DNA Deletion in an Infant with Addison Disease

Background: Mitochondrial diseases are a group of disorders caused by mutations in nuclear DNA or mitochondrial DNA, usually involving multiple organ systems. Primary adrenal insufficiency due to mitochondrial disease is extremely infrequent and has been reported in association with mitochondrial DNA deletion syndromes such as Kearns–Sayre syndrome. Aim: To report a 3-year-old boy with Addison disease, congenital glaucoma, chronic pancreatitis, and mitochondrial myopathy due to large mitochondrial DNA deletion. Method: Molecular analysis of mitochondrial DNA samples obtained from peripheral blood, oral mucosa, and muscle tissue. Results: A novel large mitochondrial DNA deletion of 7,372 bp was identified involving almost all genes on the big arch of mtDNA. Conclusions: This case reaffirms the association of adrenal insufficiency and mitochondrial DNA deletions and presents new evidence that glaucoma is another manifestation of mitochondrial diseases. Due to the genetic and clinical heterogeneity of mitochondrial disorders, molecular analysis is crucial to confirm diagnosis and to allow accurate genetic counseling. Introduction Primary adrenal insufficiency, commonly known as Addison disease, is uncommon in the Western population and is estimated to affect 90–140 per 1 million people (Arlt and Allollo 2003). The spectrum of adrenal disorders differs in childhood and adult patients. Primary adrenal insufficiency in childhood and adolescence is due to abnormalities of gland development, gland responsiveness, and either to defects of steroid biosynthesis or target organ response. Primary adrenal dysfunction associated with mitochondrial disease has been reported extremely infrequently (Boles et al. 1998) and is generally associated with mitochondrial DNA deletion syndromes such as Kearns– Sayre Syndrome (KSS). Clinical features typical of mitochondrial diseases include ptosis, progressive external ophthalmoplegia (PEO), proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. KSS has also been associated with a variety of endocrine disorders such as short stature (38%), gonadal dysfunction (20%), and diabetes mellitus (13%) (Harvey and Barnett 1992). We report the case of a boy with Addison disease associated with congenital glaucoma, chronic pancreatitis, and mitochondrial myopathy due to a large mtDNA deletion.