Generally, the first signs of APS-1 appear in childhood, with the complete development of the three main diseases occurring within the first two decades of life. However, additional associated conditions can emerge up until the fifth decade. Candidiasis is often the first symptom, usually appearing before the age of 5, followed by hypoparathyroidism before age 10, and Addison's disease typically before the age of 15. While these three main components of APS-1 tend to occur in a specific chronological order, they are only present in about one-third to one-half of the cases. The case in discussion is unique as it highlights the presence of endocrine abnormalities from the age of 7. However, the patient did not develop mucocutaneous candidiasis until their third decade. This deviates from the more common chronological pattern of APS-1 symptoms. [3]
Ectodermal dystrophy is a group of problems related to Autoimmune Polyendocrine Syndrome Type 1 (APS-1). These problems include changes in the nails, underdeveloped dental enamel (mostly in permanent teeth), hair loss, keratopathy, and vitiligo. These manifestations do not necessarily occur in all APS-1 patients. Autoimmune reactions specifically attribute alopecia and vitiligo, while chronic candidiasis often causes nail deformities. The exact cause of dental enamel hypoplasia in APS-1 remains unclear. In the discussed case report, the patient exhibited alopecia and nail dystrophy, affecting both feet and hands. Treatment for the nail dystrophy involved terbinafine lotion. [4] An autosomal recessive pattern of inheritance is observed in APS-1. Over 60 identified mutations in the AIRE gene contribute to the disease's presentation and progression variability. Notably, more than 95% of APS-1 patients have one of two common mutations: an arginine substitution at position 257 or a 13-base pair deletion in exon 8. Specific mutations in the AIRE gene have been observed in certain populations, including the R257X mutation in Finnish patients, the 1094-1106del13 deletion in British, Irish, Norwegian, and North American patients, and the Y85C missense mutation in Iranian Jewish patients. However, clear correlations between specific AIRE mutations and patient clinical outcomes remain unclear. [5, 6]
Chronic Mucocutaneous Candidiasis (CMC) usually manifests early in life, typically between 3 and 5, and is the most common of the three main diseases associated with APS-1. It affects the nails, skin, and mucous membranes of the oral cavity, vagina, and esophagus. In some instances, CMC can lead to severe complications like esophagitis, oesophagal stricture, retrosternal pain, and dysphagia. In this particular case, the patient presented with symptoms of oral mucocutaneous candidiasis, dysphagia, and dysarthria. Initiating nystatin treatment significantly improved the symptoms, underscoring the efficacy of antifungal therapy in treating oral manifestations of APS-1. Patients with APECED face a heightened risk of developing oral cancer at a younger age, even without traditional risk factors. A Finnish study found a significant incidence of squamous cell carcinoma in these patients. [3, 7] Additionally, enamel defects, such as grooves or pits, primarily in permanent teeth, are a significant oral manifestation of APECED. Patients with APS-1 often suffer from poor oral health, including increased dental caries, enamel erosion, and periodontal disease. Medication side effects and difficulties in maintaining oral hygiene due to enamel defects and persistent oral candidiasis can worsen these issues. [7]
Autoimmune polyendocrine syndrome type 1 (APS-1), also known as APECED (Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy), MEDAC (multiple endocrine deficiency autoimmune candidiasis syndrome), juvenile autoimmune polyendocrinopathy, or Whitaker syndrome, is a very rare autosomal recessive genetic condition that causes multiple organs to become autoimmunized. It is usually found in early childhood. In clinical terms, APS-1 is when at least two of the classic triad conditions are present at the same time. These are hypoparathyroidism, adrenal insufficiency, and mucocutaneous candidiasis. Additionally, it may encompass immunological disorders unrelated to the endocrine system. [8]
Mutations in the autoimmune regulator (AIRE) gene on the short arm of chromosome 21 cause Autoimmune Polyglandular Syndrome Type 1 (APS-1). This gene is crucial for producing the 'autoimmune regulator' protein, predominantly expressed in the thymus gland, which plays a vital role in developing thymus-derived T lymphocytes. T-cells can interact with self-antigens and escape into circulation instead of being destroyed in the thymus due to a deficiency in this protein. This escape can lead to autoimmunities, often affecting the endocrine glands. Researchers have acknowledged four core classifications of APS, with each category exhibiting a unique set of autoimmune endocrine abnormalities. APS-1 is characterized by chronic mucocutaneous candidiasis, primary hypoparathyroidism, and autoimmune adrenal insufficiency. Relatives of a patient can establish the diagnosis of APS-1 in the presence of any of these diseases. In type 2 autoimmune polyendocrine syndrome (APS), autoimmune adrenal insufficiency is present along with concurrent autoimmune thyroid illness and/or type 1 diabetes mellitus. The coexistence of autoimmune thyroid disease and other autoimmune disorders characterizes type 3 autoimmune polyglandular syndrome (APS). However, it is important to note that this classification specifically excludes chronic candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Type 4 (APS) refers to instances where individuals present with two or more autoimmune disorders specific to certain organs but do not satisfy the requirements for Types 1, 2, or 3 APS. [8]
This case report details a 27-year-old man born from a consanguineous marriage with a medical history including alopecia, intellectual disability, epilepsy, hypothyroidism, type 1 diabetes, and dilated cardiomyopathy, starting at age 7. His chief complaints upon presentation were dysarthria, dysphagia, and lethargy. A general examination revealed oral candidiasis, nail dystrophy in both upper and lower limbs, and alopecia. The tests showed that the person had anemia (hemoglobin 2.7 g/dl), low calcium levels (5.3 mg/dl), low parathyroid levels (PTH 3.0 pg/ml), and calcifications on both sides of the white matter in the frontal, parietal, temporal, and basal ganglia. Together with the mucocutaneous candidiasis and hypoparathyroidism found, these results led to the diagnosis of Autoimmune Polyendocrine Syndrome Type 1 (APS-1). This case is unique in its combination of multiple autoimmune and endocrine issues. Despite his conditions, the patient wasn't severely ill until the development of dysarthria and dysphagia, which prompted a visit to a local physician and subsequent referral to the reporting institute.
In our case, the patient has presented with seizures since age 7, and the most notable finding was an MRI showing the presence of bilateral basal ganglia/thalamic calcification. Fahr syndrome is a rare neurological disorder characterized by the deposition of calcium compounds in the basal ganglia, thalamus, dentate nucleus, hippocampus, cerebral cortex, and cerebellar subcortical white matter. The calcium deposits are usually calcium carbonate and calcium phosphate. The exact etiology of the disease is not known but is usually associated with endocrine-affecting calcium homeostasis, mitochondrial myopathies, dermatological abnormalities, and infectious diseases. A prevalent clinical presentation of Fahr syndrome is seizures. Patients also present with other neurological symptoms of the extrapyramidal system, neuropsychiatric abnormalities, and movement disorders like Parkinsonism, tremors, and chorea.