Six year old with autoimmune polyglandular syndrome: can genetics tell us the story?
ABSTRACT Children who have diabetes mellitus type 1 (DMT1) are at increased risk of developing other autoimmune diseases. These associated diseases include Hashimoto's thyroiditis, Graves' disease, Celiac disease, and Addison's disease. Since Addison's disease is potentially fatal if undiagnosed and untreated, it would be prudent to effectively screen individuals to determine if they are at risk of developing this disease. We present a case of a 6 year old male with a history of DMT1, who presented in adrenal crisis and was subsequently diagnosed with Addison's disease. HLA-DRB1 404/DR4 is one of the genes involved in the development of Addison's disease in children with DMT1. Our patient later tested positive for this haplotype. Genetic testing is not routinely done in patients with (DMT1) to determine if they will potentially develop other associated conditions. We propose using genetic testing of associated HLA haplotypes to screen children with DMT1 for Addison's disease.
- SourceAvailable from: Brian M Freed[show abstract] [hide abstract]
ABSTRACT: Of 957 patients with type 1 diabetes without known Addison's disease 1.6% (n = 15) were positive for 21-hydroxylase autoantibodies. Among DQ8/DQ2 heterozygous patients, the percentage expressing 21-hydroxylase autoantibodies was 5% (10 of 208) vs. less than 0.5% of patients with neither DQ8 nor DQ2. Three of the diabetic patients found to have 21-hydroxylase autoantibodies on screening were subsequently diagnosed with Addison's disease. Overall, the genotype DQ8/DQ2, consisting of DRB1*0404/DQ8 with DRB1*0301/DQ2, was present in 14 of 21 patients with Addison's disease (8 of 12 with diabetes and 6 of 9 without diabetes or antiislet autoantibodies) vs. 0.7% of the general population (109 of 15,547; P < 10(-6)) and 11% of patients with DM without Addison's disease (62 of 578; P < 10(-6)). Among patients with diabetes with DQ8, Addison's disease was strongly associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB1*0404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patients, 80% with DRB1*0404 (12 of 15) had Addison's disease, in contrast to 1 of 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P < 0.001). We conclude that patients with DRB1*0404 and 21-hydroxylase autoantibodies are at high risk for Addison's disease. Patients with DRB1*0401 and DRB1*0402 have more limited progression to Addison's disease despite the presence of 21-hydroxylase autoantibodies.Journal of Clinical Endocrinology & Metabolism 02/1999; 84(1):328-35. · 6.43 Impact Factor
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Article: Autoimmune polyendocrine syndromes.New England Journal of Medicine 06/2004; 350(20):2068-79. · 51.66 Impact Factor