Early testing for adrenal insufficiency may justify early use of glucocorticoids and mineralocorticoids. Acknowledgments The authors thank the Children’s Mercy Medical Writing Center at Children’s Mercy Hospital for editing this manuscript. 12, she was given 2 doses of rituximab. Hair loss rapidly progressed to alopecia totalis and then to alopecia universalis, at which time oral methotrexate treatment was initiated. For the past 7 years while on glucocorticoid and methotrexate treatment, our patient has displayed normalization of 2 antibodies, a lack of progression to additional autoimmune diseases, and experienced reversal of alopecia universalis. 1. Introduction Autoimmune polyglandular syndrome type 1 (APS1), also known as APECED (autoimmune polyendocrinopathy candidiasis ectodermal dysplasia), is a rare but serious disorder associated with progressive autoimmune destruction of multiple endocrine and nonendocrine organs. APS1 has a high mortality rate. The median age at death ranges from 5 to 34 years, with deaths attributable to endocrinopathies, malignancy, acute hepatitis, and infection [1]. APS1 is caused by biallelic variations of the gene encoding the autoimmune regulator (AIRE), resulting in dysfunction of regulatory T cells, impaired immunologic tolerance to Vancomycin hydrochloride self-antigens with subsequent development of multiple autoimmune conditions [2]. Immunosuppressive therapies have been generally reserved for Mouse monoclonal to GFI1 life-threatening features of APS1. To the best of our knowledge, this is the first case report demonstrating normalization of serology, reversal of an autoimmune condition, and prolonged lack of progression of autoimmune damage in APS1. 2. Case Report The patient was a previously healthy 6-year-old girl of northern European descent whose only concerns had been enlarged tonsils, chronic constipation, and slow growth. She had no other health problems. There was no family history of endocrine Vancomycin hydrochloride or immunologic diseases. While watching television, she developed a grand mal seizure and became apneic. She was emergently transported to Children’s Mercy Hospital. Initial physical examination was unremarkable except for short stature, with weight 20?kg (37.7 percentile) and height 104.6?cm (less than the 1st percentile). Family history revealed that the patient’s mother is 162.6?cm tall and father is 177.8?cm tall; midparental height is 167.7?cm (50th percentile). She was found to have a critically low total calcium of 1 1.1?mmol/L (normal range 2.2C2.5?mmol/L) and a blood glucose of 3.6?mmol/L (normal range 3.6C6.1?mmol/L). Her phosphorus was elevated at 3.6?mmol/L (1C1.9?mmol/L), and magnesium was low at 0.49?mmol/L (0.66C0.94?mmol/L). Initial iPTH level was low at 7?ng/L (10C89?ng/L), and subsequent iPTH levels remained low. She was diagnosed with primary hypoparathyroidism. She received intravenous calcium chloride and magnesium sulfate. Computed tomography of the head was normal. An extensive Vancomycin hydrochloride endocrine workup revealed that she had Howell-Jolly bodies consistent with autoimmune hyposplenism, a condition frequently seen in APS1 [3]. No other autoimmune deficiencies were noted at that time. Karyotype was 46, XX. Evaluation of 22 q 11 variants was normal. A growth hormone (GH) stimulation test was performed during initial admission. Her peak GH level was 12.8?ng/mL (normal 10?ng/mL). With the documentation of two unusual autoimmune findings, genetic testing for AIRE gene was performed. The patient was found to be a compound heterozygote for 2 known disease-causing variants. The first was a nucleotide change of C? ?T in exon 6 of the AIRE gene resulting in the substitution of the normal arginine codon with a stop codon at position 257. This mutation is denoted R257X or Arg257Term. The second mutation was a 13 base-pair deletion in exon 8, beginning in codon leucine 323 and resulting in a change from leucine to serine, followed by a frameshift and premature stop codon 50 residues downstream (denoted c.967 979del13 and p.Leu323SerfsX50). Thus, she was heterozygous for R257X and c.967 979del13. Both are common, independently recurring mutations in APS1 [4]. The 13-base deletion has been published with various nomenclature (c.965 977del13 or p.Cys322fsX5l). After testing positive for AIRE gene variants, additional serologic testing revealed seropositivity for 21-hydroxylase antibodies (a marker for adrenal autoimmunity) and positivity for intrinsic factor autoantibodies (a marker for atrophic gastritis). Figure 1(a) shows her positive serology over time, along with her immunosuppressive medications. Antibody testing for thyroid disease, type 1 diabetes mellitus, and celiac disease yielded negative results at that time. Open in a Vancomycin hydrochloride separate window Figure 1 Timeline of development of autoantibodies (a), autoimmune processes (b), and smooth muscle and SSA antibodies (c) with time course of known immunosuppressive therapy also shown. At the age of 6 and a half years, a low-dose ACTH stimulation test showed a borderline peak cortisol of 433?nmol/L (normal 500?nmol/L). ACTH stimulation testing was repeated a year later, at which time, she demonstrated a peak cortisol level of.