PSAT204 Hypoparathyroidism due to a Novel Mutation as the Initial Presentation of Non-classical Autoimmune Polyglandular Syndrome Type 1
Authors: Cromer David , Sinnott Bridget 
Published: November 2022

Background

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder, with an estimated worldwide prevalence of 1 in 80-100,000, resulting from a mutation in the autoimmune regulator (AIRE) gene responsible for immune tolerance. It is characterized by the presence of 2 or 3 cardinal disorders – primary adrenal insufficiency, chronic mucocutaneous candidiasis, and hypoparathyroidism. It is now known that APS-1 presents in 2 forms – the classic autosomal recessive form, which presents early in life with at least 2 of 3 components of the clinical triad, and the non-classical form, which is caused by a dominant heterozygous mutation and usually presents later in life with a milder clinical phenotype and incomplete penetrance.Clinical case:A 29-year-old African American female presented to the clinic with symptoms of twitching, cramping, and paresthesias. She was diagnosed with hypoparathyroidism at age 18 years, which was complicated by hypocalcemic seizures. She was taking calcium and calcitriol with fluctuating calcium levels. Other medical problems included hypertension and anxiety. She denied having frequent infections or history of autoimmune disorders. She reported regular menses. Her family history was negative for autoimmune disease and calcium disorders. Physical examination revealed a well-developed woman with unremarkable vitals and BMI 35.9 kg/m2. She had positive Chvostek's sign bilaterally, negative trousseaus sign, 2+ reflexes throughout and normal gait. She had no onychomycosis, mucocutaneous candidiasis, hyperpigmentation, or vitiligo. She had a normal cardiac, respiratory, and abdominal examination. Lab work up was remarkable for calcium 6.4 mg/dL (8.1-10.4), PTH 6 pg/mL (11.1-79.5), eGFR 104 ml/min/m2 (normal: &gt;90), 24-hour urinary calcium (&lt;1 mg/24hours) & creatinine 1.0 g/24hours, vitamin D25-OH 26.23 ng/ml (25-80), magnesium 1.7 mg/dL (1.3-2.7), vitamin B12 level 445 pg/mL (211-911) and TSH 2.243 mcIU/mL (0.4-4.7). She had negative antibodies to TPO, TTG IgA, 21-hydroxylase, IA-2, and GAD65. Plain films did not identify intracranial calcifications or nephrolithiasis. Genetic evaluation revealed a heterozygous mutation in the AIRE gene c.718 G&gt;A in exon 6, p.G240S consistent with non-classic APS-1.

Conclusion

This case highlights the importance of genetic testing in patients with isolated hypoparathyroidism. Our case had a novel mutation (c.718 G&gt;A) in the SAND domain of the AIRE gene, in contrast to the majority of prior non-classical APS-1 mutations which are localized to the 1st plant homeodomain (PHD-1) of AIRE gene. It is important to report the clinical features of these patients with novel mutations as it can enrich our understanding and contribute to future research. It is important to establish a diagnosis of APS-1, as these patients are at risk for both endocrine and other autoimmune manifestations which may manifest during its natural history.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.