Summary

Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison’s disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison’s disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex.

Learning points:

• Autoimmune polyglandular syndrome type 1 (APS-1) is a deeply heterogeneous genetic entity with a broad spectrum of clinical manifestations and a significant intra-family phenotypic variability.

• Early diagnosis of APS-1 is challenging but clinically relevant, as endocrine and non-endocrine manifestations may occur during its natural history.

• APS-1 should be considered in cases of acquired hypoparathyroidism, and even more so with manifestations with early onset, family history and consanguinity.

• APS-1 diagnosis needs a high index of suspicion. Key information such as all the comorbidities and family aspects would never be valued in the absence of a complete clinical history taking.

• Especially in hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex and is not a matter of simply approaching individually each condition.

• Regular long-term monitoring of APS-1 is essential. Intercalary contact by phone calls benefits the control of the disease and the management of complications.