What is the most common diagnosis in a patient with Autoimmune Polyendocrinopathy (Autoimmune Polyendocrinopathies, APECED) syndrome, presenting with multiple cranial neuropathies?

From the Guidelines

The most common diagnosis in a patient with autoimmune polyendocrinopathy, ectodermal dysplasia, and mucocutaneous candidiasis (APECED) presenting with multiple cranial neuropathies is likely autoimmune hypocalcemia due to hypoparathyroidism. The multiple cranial neuropathies are explained by hypocalcemia causing increased neural excitability and dysfunction of cranial nerves. Hypoparathyroidism leads to decreased calcium levels, which impairs normal nerve function and can manifest as paresthesias, tetany, and cranial nerve abnormalities. Treatment involves calcium supplementation (typically calcium carbonate 1000-2000 mg elemental calcium daily in divided doses) and active vitamin D (calcitriol 0.25-1 mcg daily) 1. Serum calcium levels should be maintained in the low-normal range (8.0-8.5 mg/dL) to prevent symptoms while avoiding hypercalciuria. Regular monitoring of calcium, phosphorus, and urinary calcium excretion is essential. APECED, also known as Autoimmune Polyendocrine Syndrome Type 1, is caused by mutations in the AIRE gene, which regulates self-tolerance 1. Hypoparathyroidism is one of the earliest and most common manifestations, affecting up to 80% of patients with APECED, and prompt correction of calcium levels typically leads to resolution of neurological symptoms. Imaging studies, such as MRI, may be useful in evaluating cranial neuropathy, particularly in detecting potential intraparenchymal or extraparenchymal processes 1. However, in patients with APECED, the primary focus should be on managing the underlying autoimmune and endocrine abnormalities, rather than solely relying on imaging studies.

Some key points to consider in the management of APECED include:

• Prompt recognition and treatment of hypoparathyroidism to prevent neurological symptoms
• Regular monitoring of calcium, phosphorus, and urinary calcium excretion to avoid hypercalciuria
• Use of calcium supplementation and active vitamin D to maintain serum calcium levels in the low-normal range
• Consideration of imaging studies, such as MRI, to evaluate cranial neuropathy and detect potential underlying processes
• Management of other autoimmune and endocrine abnormalities associated with APECED, such as adrenal insufficiency and gonadal failure.

Overall, the management of APECED requires a comprehensive approach that takes into account the patient's underlying autoimmune and endocrine abnormalities, as well as their neurological symptoms. By prioritizing the management of hypoparathyroidism and other associated conditions, clinicians can help improve outcomes and quality of life for patients with APECED.

From the Research

Diagnosis and Clinical Features

• The most common diagnosis in a patient with autoimmune polyendocrinopathies, ectodermal dysplasia, and mucocutaneous candidiasis is Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome 2, 3, 4, 5, 6.
• APECED syndrome is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE) 2, 3, 4, 5, 6.
• The classic triad of APECED syndrome includes chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency 3, 4, 5, 6.

Multiple Cranial Neuropathies

• There is no direct evidence in the provided studies that explains the multiple cranial neuropathies in a patient with APECED syndrome.
• However, APECED syndrome is characterized by a wide range of autoimmune manifestations, including non-endocrine organ involvement 4.
• It is possible that the multiple cranial neuropathies are a rare or atypical manifestation of APECED syndrome, but further research is needed to confirm this association.

Clinical Presentation and Diagnosis

• APECED syndrome usually begins in childhood, with chronic mucocutaneous candidiasis being the first manifestation to appear, usually before the age of 5 years 5.
• The clinical phenotype of APECED syndrome may evolve over several years, and many components of the disease may not appear until the 4th or 5th decade of life 5.
• An early diagnosis of APECED syndrome can be challenging due to the wide variability in clinical presentation, even among siblings with the same genotype 5, 6.