Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome

Abstract

Objective: To characterize the endocrine and autoimmune disturbances with emphasis on parathyroid dysfunction in patients with 22q11.2 deletion syndrome (22q11.2 DS). Design: In this nationwide survey; 59 patients (age 1-54 years) out of 86 invited with a 22q11.2 DS were recruited through all the genetic institutes in Norway. Methods: Data was collected from blood tests, medical records, a physical examination and a semistructured interview. We registered autoimmune diseases and measured autoantibodies, hormone levels and HLA types. Results: Twenty-eight (47%) patients had hypoparathyroidism or a history of neonatal or transient hypocalcemia. Fifteen patients had neonatal hypocalcemia. Fourteen patients had permanent hypoparathyroidism including seven (54%) of those above age 15 years. A history of neonatal hypocalcemia did not predict later occurring hypoparathyroidism. Parathyroid hormone levels were generally low indicating a low reserve capacity. Twenty-eight patients were positive for autoantibodies. Six (10%) persons had developed an autoimmune disease, and all were females (P!0.02). Hypoparathyroidism correlated with autoimmune diseases (P!0.05), however, no antibodies were detected against the parathyroid glands. Conclusions: Hypoparathyroidism and autoimmunity occur frequently in the 22q11.2 DS. Neonatal hypocalcemia is not associated with later development of permanent hypoparathyroidism. Hypoparathyroidism may present at any age, also in adults, and warrants regular measurement of calcium levels. Hypoparathyroidism and autoimmunity occur frequently together. Our findings of autoimmune diseases in 10% of the patients highlight the importance of stringent screening and follow-up routines.

An Adult Case of 22q11.2 Deletion Syndrome Diagnosed in a 36-year-old Woman with Hypocalcemia Caused by Hypoparathyroidism and Hashimoto's Thyroiditis

“…Indeed, Gennery et al reported autoimmune disorders or detectable autoantibodies in 33% of children with 22q11.2 deletion syndrome (18), while Lima et al observed autoimmune thyroid disease in three of 10 patients above 17 years of age, which is higher than the incidence observed in the general population in Norway (6). Although there are differences between races, for example Choi et al showed that autoimmune thyroid diseases occurred in only two (3.3%) of 66 patients with 22q11.2 deletion syndrome in Korea (19), these results suggest that the incidence of autoimmune thyroid disease in adults with this syndrome is higher than that observed in the general adult population.…”

“…It is associated with a typical facial appearance and clinical symptoms and findings such as congenital heart defects, immune deficiency caused by thymic hypoplasia, palatal cleft and mental retardation (2,4,5). In addition, autoimmunity is more common in affected patients than in the general population (6).…”

“…A range of autoimmune features associated with 22q11.2 deletion syndrome have been described, including cytopenia and disorders of systemic autoimmunity, particularly rheumatoid arthritis and autoimmune thyroid disease (6). This syndrome typically becomes apparent in early childhood and is rarely diagnosed in adulthood (7)(8)(9).…”

Two Cases of 22Q11.2 Deletion Syndrome and Type 1 Diabetes

“…Those with two or more pancreatic autoantibodies are now considered stage 1 (preclinical) disease and have a 68% risk of developing clinically evident disease (dysglycemia with or without symptoms) within 5 years, and for those with three or more pancreatic antibodies, this risk increases to 100% (15,16). A study evaluating the presence of autoantibodies in pediatric and adult patients with 22q11.2DS reported that 5 of 28 patients had 1 to 2 pancreatic autoantibodies, but none had developed T1D at the time of publication (17). This brings to light the notion of a potential protective mechanism in patients with 22q11.2DS, in contrast to the possibility that these patients are at high risk of developing T1D in the future.…”

Federal clinical recommendations on diagnostics and treatment of hypoparathyroidism in the children and adolescents

“…-ЭКГ; -рентгенография черепа, грудной клетки, ко-стей таза, нижних конечностей 2 ; -офтальмологический осмотр 3 ; -КТ головного мозга 4 [BIII]. Оценка результатов лабораторного обследования Низкий уровень кальция в сочетании с высо-ким уровнем фосфора является диагностическим критерием гипопаратиреоза.…”