medwireNews: Children with autoimmune polyendocrine syndrome (APS)1 have highly variable clinical findings, and often present with nonendocrine features, shows analysis of a Norwegian cohort.

Although 32% of the 52 patients presented with hypoparathyroidism, 25% had chronic mucocutaneous candidiasis (CMC) as their presenting symptom. And although not a common presenting symptom, enamel hypoplasia eventually developed in 72% of the 25 children who were examined by a dentist.

The appearance of these symptoms in childhood should therefore “trigger further diagnostic workup”, say Eystein Husebye (University of Bergen) and study co-authors.

The “classic triad” of APS1 manifestations are hypoparathyroidism, CMC and primary adrenal insufficiency, and these eventually developed in 73%, 77% and 63% of patients, respectively. Although 40% of patients developed all three manifestations, only 67% did so by the age of 25 years.

However, the researchers note many differences from previously published cohorts. For example, 19% of their patients had hypothyroidism, which did not appear in Sardinian patients, but they found only two (4%) cases of autoimmune hepatitis, despite this appearing in nearly a third of the Sardinian cohort.

But Husebye et al note that previous cohorts came from “populations with strong founder effects”.

They say: “The Norwegian population displays a greater genetic heterogeneity and may therefore be more representative for the situation in most countries.”

Other fairly common manifestations in the Norwegian patients were malabsorption, alopecia and gonadal failure, occurring in 23% to 33% of patients.

Fifteen patients died, and seven of these were diagnosed with APS1 only after their deaths, including the five youngest patients, who died between the ages of 3 and 17 years.

“This underscores the importance of increased awareness and early diagnosis”, writes the team in The Journal of Clinical Endocrinology & Metabolism. “APS1 should be considered in all patients presenting one of the major clinical manifestations, especially when it presents in childhood.”

They also stress that the siblings of a deceased patient should be tested, in case of late onset. The patients in their study ranged from an age of 0 to 43 years at onset.

Autoantibodies against interferon (IFN)ω were present in 42 (93%) of 45 patients tested. Two of the other three patients had neither IFNω autoantibodies nor mutations in the autoimmune regulator gene (AIRE), and the team suggests these patients could have had mutations affecting AIRE regulation or other genes in the same pathway. However, the third patient lacked IFNω autoantibodies despite being compound heterozygous for two AIRE mutations.

The researchers therefore stress that the absence of IFNω autoantibodies does not exclude APS1, and advise sequencing the AIRE gene if clinical suspicion is high.

By Eleanor McDermid

J Clin Endocrinol Metab 2016; Advance online publication

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