When One Gland Speaks First: Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1) Unmasked by Isolated Hypoparathyroidism

TL;DR

A child with isolated hypoparathyroidism was later diagnosed with APS-1, a rare autoimmune disorder, highlighting the importance of early genetic testing.

Contribution

This case demonstrates that APS-1 can present with isolated hypoparathyroidism for years before other symptoms appear.

Findings

Isolated hypoparathyroidism can precede other APS-1 features by several years.

A homozygous likely pathogenic AIRE gene mutation was identified in the patient.

Early genetic testing enables proactive management of APS-1.

Abstract

Autoimmune polyendocrinopathy syndrome type 1 (APS-1) is a rare autosomal recessive disorder caused by pathogenic variants in the AIRE gene and classically characterized by the triad of hypoparathyroidism, chronic mucocutaneous candidiasis, and adrenal insufficiency. Although hypoparathyroidism is often the earliest manifestation, isolated and prolonged monosymptomatic presentations remain uncommon and may delay recognition of the syndrome. We report the case of a child who was first presented at four years of age with severe hypocalcemia in the setting of acute gastroenteritis and was diagnosed with hypoparathyroidism. Apart from hypomagnesemia and hyperphosphatemia, extensive workup revealed no additional autoimmune or endocrine abnormalities. Genetic testing subsequently identified a homozygous likely pathogenic stop-loss AIRE gene mutation, confirming APS-1. Over a three-year follow-up period, the patient remained clinically stable with well-controlled hypoparathyroidism, except for hypocalcemic episodes during diarrheal illnesses, and persistently normal adrenal, thyroid, pancreatic, and celiac screening. The first additional disease feature emerged three years after the initial presentation, at the age of seven years, when a fungal nail infection consistent with mucocutaneous candidiasis was noted. This case highlights the marked phenotypic variability with delayed evolution of APS-1 and underscores that isolated hypoparathyroidism, even when severe, may precede other disease components by several years. Early genetic testing in children with apparently isolated hypoparathyroidism allows anticipatory guidance, structured surveillance, and timely recognition of evolving autoimmune manifestations.

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