Patients with PGA-I often have gastrointestinal manifestations such as autoimmune gastritis, autoimmune hepatitis, and malabsorption. Hyposplenism and asplenia are also common unexplained features. In many cases, dental enamel hypoplasia, keratoconjunctivitis, vitiligo, alopecia, nail pitting, and/or tympanic membrane calcifications are also present. Most patients will exhibit 3-7 different manifestations early in the course of the disease, but other components may appear throughout life.[7,8]
PGA-I is a very rare disorder. In Finland, where the highest number of cases of PGA-I have been reported, the estimated prevalence is about 1 in 25,000 inhabitants. In the majority of cases, the syndrome occurs in childhood. The female-to-male ratio varies in different reports from 0.8-1.5. In Italy, only a few case reports have been described to date.
Patients with PGA-I have loss-of-function mutations in the autoimmune regulator gene, located on chromosome 21q22.3.[9,10] Patients with PGA-I have demonstrable circulating antibodies directed against a wide range of self-antigens, most with a restricted tissue distribution corresponding to the affected organs. The majority of patients have antibodies against enzymes involved in the steroid biosynthesis and hepatic metabolism of xenobiotics. Because a large variation in phenotype and presentation has been recognized (even in siblings), the traditional clinical definition does not identify all patients. Mutational analysis of the AIRE gene (eg, R257X mutation) may help in identifying such patients with atypical presentations.
The clinical presentation of PGA component diseases is often preceded by an asymptomatic latent period of months or years characterized by the presence of circulating disease-associated antibodies. Autoantibodies are useful markers for predicting the development of PGA. The absence of these antibodies does not exclude the disease because not all patients show positive antibodies. The present long-term follow-up data emphasize that the detection of these antibodies facilitates early diagnosis of autoimmune endocrine disorders. In view of the possible long time interval between manifestation of the first autoimmune endocrinopathies and subsequent manifestations, regular and long-term observation of patients with autoimmune endocrine disorders seems necessary.
For patients with monoglandular autoimmune endocrinopathy, functional screening for PGA is recommended once every 3 years until age 75 years. If pathologic findings of a second autoimmune endocrine disease are noted, measurement of organ-specific autoantibodies should be added. Furthermore, functional screening for autoimmune endocrine diseases of first-degree relatives of patients with newly diagnosed PGA may also be done. Serologic testing for the presence of diabetes-associated antibodies should especially be considered in the offspring of patients with type 1 diabetes. According to the literature, genetic screening may only be useful in PGA-I.
Medscape © 2022 WebMD, LLC
Cite this: 17-Year-Old With Hair Loss, Dysmenorrhea, Thrush, and Diarrhea - Medscape - Mar 15, 2022.