title: Sideroblastic anaemia and primary adrenal insufficiency due to a mitochondrial respiratory chain disorder in the absence of mtDNA deletion.
abstract: A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin.
authors.affiliation: Department of Paediatrics, Midland Regional Hospital, Mullingar, Ireland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Grady
authors.affiliation: National Centre for Inherited Metabolic Disorders, Children's University Hospital, Dublin, Ireland.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Monavari
authors.affiliation: Department of Paediatric Haematology, Children's University Hospital, Dublin, Ireland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cotter
authors.affiliation: Department of Paediatric Endocrinology, Children's University Hospital, Dublin, Ireland.
authors.forename: Nuala P
authors.initials: NP
authors.lastname: Murphy
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D000756:Anemia, Sideroblastic / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000175:diagnosis*; D019988:Children with Disabilities; D005198:Fanconi Syndrome / Q000175:diagnosis* / Q000503:physiopathology; D005221:Fatigue / Q000209:etiology*; D019270:Fructosamine / Q000008:administration & dosage; D005938:Glucocorticoids / Q000008:administration & dosage; D020249:Hormone Replacement Therapy; D006801:Humans; D007004:Hypoglycemic Agents; D000069057:Insulin Detemir / Q000008:administration & dosage; D008297:Male; D008901:Mineralocorticoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004272:DNA, Mitochondrial; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D008901:Mineralocorticoids; D019270:Fructosamine; D000069057:Insulin Detemir