Hypoparathyroidism and insulin‐dependent diabetes mellitus in a patient with Kearns–Sayre syndrome harbouring a mitochondrial DNA deletion

Abstract

We report a 17-year-old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns-Sayre syndrome). A large-scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin-dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24-30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C-peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA-A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns-Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.

Recognition of mitochondrial DNA deletion syndrome with non-neuromuscular multisystemic manifestation

“…Thirteen reports were single patient cases with various clinical presentations. 8,9,11,15,16,[22][23][24][25][26][27][28][29] One report had 4 patients with hypoparathyroidism, 17 another had 7 patients with KSS, 3 one had 3 patients with Pearson syndrome, 14 one had 2 patients with multiple endocrine problems, 6 and another had 20 KSS patients. 19 Overall, 34 patients had typical KSS, CPEO, or MM, 14 patients had multisystemic disorders with initial presentation of non-neural, nonmuscular clinical manifestations.…”

“…Recently, mtDNA deletion syndromes have been reported in patients with various clinical manifestations, including Addison disease, 6 -8 atypical Pearson presentation, 9 -11 cyclic vomiting, 6,9,12 severe renal tubulopathy, 11 hepatic dysfunction, 13 dysarthria, 9,10 organic acidopathy, 14,15 and hypoparathyroidism and hypocalcemia. 6,16,17 The mitochondrial DNA deletion syndrome is defined as any case with a single mtDNA deletion, regardless of the clinical phenotype. In KSS, deleted mtDNA occurs mainly in muscle and not always in leukocytes.…”

Severe Hypomagnesemia and Hypoparathyroidism in Kearns-Sayre Syndrome

“…Magnesium depletion may lead to hypoparathyroidism either by suppression of PTH secretion or production of ineffective circulating hormone [8]. However, in our case even though magnesium depletion was partially improved, PTH levels remained extremely low.…”

“…Mitochondrial biochemical derangements may trigger the onset of this dysfunction by reducing ATP production; an autoimmune etiology has also been implicated but not strongly enough supported [2]. Moreover, of 2 autopsied hypoparathyroid cases with KSS, 1 had absent glands while in the other only one gland could be identified by microscopic examination [8]. No study showed evidence of dietary, malabsorption or metabolic vitamin D disorders or autoimmune mechanisms.…”

Diabetes Mellitus, Deafness, Muscle Weakness and Hypocalcemia in a Patient with an A3243G Mutation of the Mitochondrial DNA.

“…The parathyroid gland may also be vulnerable to mutations in mtDNA because its function requires a high energy supply. In fact, idiopathic hypoparathyroidism has been described in another mitochondrial encephalomyopathy, Kearns-Sayre syndrome (14)(15)(16)(17), as well as in diabetic patients with an A3243G mutation of mtDNA (18,19 may also be necessary to examine mutations in the mtDNAof individuals with idiopathic hypoparathyroidism, especially those with a family history of the disease and/or with diabetes mellitus or impaired hearing.…”