Male, 20 years old, Han nationality, Shanxi origin, was first diagnosed in February 2001 for 10 years of hair loss, 8 years of episodic twitching, and 1 year of skin darkening. At the age of 10, the patient had hair and eyebrow loss within 7-8 days for no apparent reason, without fever or other discomfort, and had not grown since then, and at the age of 12, he slowly developed hand and foot numbness and occasional hand and foot convulsions, which lasted for several minutes and then relieved on their own, the degree of convulsions was mild at the beginning, but later there were daily episodes lasting for more than 10 minutes. When he was 19 years old, he gradually developed dark skin, accompanied by obvious weakness and poor nutrition, frequent nausea and vomiting, and a preference for salty food, and was twice diagnosed with adrenal crisis in a foreign hospital due to nausea, vomiting, diarrhea and fever. The patient had poor physical strength for the past 10 years, poor memory, dropped out of school at the age of 12, poor appetite, usually liked salty food, slept well, no abnormal bowel movements, no obvious chills, occasional seminal emission. He was born at full term and had no abnormalities at birth, was breastfed, and had a mouth ulcer before he was 2 years old. He had tinea capitis when he was young and was prone to catching colds; after the age of 10, he grew more slowly than children of the same age. The parents are 4th generation aunt cousins, both medium build (173cm and 167cm), fit, one sister 22 years old, one sister 14 years old, both fit, no history of convulsions, menstruation are normal. Physical examination: T:36.5ºC P:70 beats/min R: 20 beats/min BP: 90/50 mmHg (1 mmHg=0.133 kpa) Height 158 cm Weight 45 kg Normal development, malnutrition, chronic disease appearance, generalized skin and mucous membrane obvious darkening, most obvious in the lips, gums, areola and knees, elbows and finger joints extensor side, peripheral superficial lymph nodes are not large The peripheral superficial lymph nodes are not large. The hair and eyebrows were all lost, and there was no axillary or pubic hair. The eyelids were not edematous, the sclera was not yellowish, the conjunctiva was not pale, the gross visual acuity was normal, the ears and nose were not abnormal, there was no beard, the mouth and lips were dark, the mucosa was not broken, the teeth were sparse and not loose, the gums were not overflowing with pus, the pharynx was not congested, the tonsils were not large, the laryngeal nodes were prominent, the trachea was in the middle, the thyroid was not large, the jugular vein was not angry, the breath sounds in both lungs were clear, no dry wet rales were heard, the heart rate was 70 beats per minute, the rhythm was uniform, no murmur was heard. The liver and spleen were not palpable, the penis was 7 cm long with erection, the left and right testes were 7.5 ml and 8.5 ml respectively, there was no percussion pain in the bilateral kidney area, there was no deformity in the spine and limbs, no redness or swelling in the joints, and the movement was free. The muscle strength of the extremities was normal, the tendon reflexes were normally present, and Trousseau’s sign and Chvostek’s sign were positive. The hemoglobin was 117 g/L, erythrocytes 3.73×1012/L, leukocytes 17.1×109/L, urine and stool were normal, sodium 124 mmol/L, potassium 4.4 mmol/L, calcium 0.95 mmol/L, phosphorus 2 mmol/L, alkaline phosphatase 60 IU/L, blood glucose 3.8 mmol/L. Liver and kidney function was normal. Parathyroid hormone <1.0 ng/dl (normal value <55), calcitonin 27.8 pg/ml, adrenocorticotropic hormone 1007 pg/ml (normal value <46), blood cortisol 8am 1.5 ng/dl, 24-hour urinary free cortisol 6.2 ng/24h (normal value 20-72), normal thyroid function, luteinizing hormone 3.5 mIU/L ( Normal values were 4.8±0.04), follicle stimulating hormone 2.4 mIU/L (normal value 6.8±0.2), Testosterone 19 nmol/L (normal value 9.4-37). 75 g glucose tolerance test was normal, plasma albumin 4.6 g/L, globulin 3.7 g/L, immunoglobulin IgG 17.1 g/L (6-16), IgA 0.49 g/L ( 0.2-5.0), IgM 1.65 g/L (0.6-2.0). Autoantibodies: anti-adrenal antibody, islet cell antibody, glutamic acid decarboxylase antibody, thyroglobulin antibody, thyroid peroxidase antibody, anti-nuclear antibody, anti-mural cell antibody, liver and kidney microsomal antibody, smooth muscle antibody, mitochondrial antibody, acetylcholine receptor antibody and anti-RNP, Sm, ssA and ssB antibodies were negative. HLA-DR3 and HLA-DR4 were negative. Ultrasound showed that the liver was 1.4 cm below the rib cage with homogeneous echogenicity, the spleen was 4.0 cm thick, the gallbladder had multiple small strong echogenicity and gallstones, the pancreas, spleen and kidneys were not abnormal, the thyroid gland was normal in size, and multiple hypoechoic areas of about 0.3-05 cm in diameter were seen in the parathyroid area bilaterally, and the possibility of enlarged parathyroid glands was considered. CT of the adrenal glands suggested that the bilateral adrenal glands were smaller than normal, and CT of the head showed calcification of the pallidum. Diagnosis: autoimmune polyendocrine adenopathy syndrome type I, primary hypoparathyroidism, primary hypoadrenocorticism, allodynia, cholelithiasis. The patient was given hydrocortisone 20 mg in the morning and 10 mg in the evening, orally twice a day, elemental calcium 1200 mg/day, rocalciferol 0.50 μg twice a day, and the blood calcium rose to 2.25 mmol/L after two weeks without further convulsions, and the blood sodium 138 mmol/L. He felt significantly better than before, and was discharged 3 weeks later with outpatient follow-up. Analysis and discussion: The patient was a 20-year-old male with hypocalcemic convulsions at the age of 12. Laboratory tests indicated hypocalcemia, hyperphosphatemia, low blood PTH, head CT showed calcification of pallid spheres, and the diagnosis of primary hypoparathyroidism was clear; there was significant skin and mucous membrane pigmentation, accompanied by significant weakness, poor appetite, nausea and vomiting symptoms and hyponatremia, hypotension, and blood urine cortisol levels were significantly lower than normal. The diagnosis of primary hypoadrenocorticism was clear; the presence of primary hypoparathyroidism and primary hypoadrenocorticism, together with the presence of oral ulcers, ringworm of the head and ringworm of the feet in childhood, were consistent with the clinical manifestations of autoimmune polyendocrine adenopathy syndrome type I, and the diagnosis was established; total baldness was considered to be related to autoimmunity of the scalp; despite the absence of beard and pubic hair Despite the absence of beard and axillary hair, the patient had ejaculation and erection, prominent laryngeal nodes, normal testosterone and LH and FSH levels, indicating no gonadal involvement; normal glucose and glucose tolerance tests, negative antibodies to islet cells and glutamic acid decarboxylase, suggesting no endocrine involvement of the pancreas; negative autoantibodies to the thyroid gland and normal thyroid function, suggesting no thyroid involvement; the patient's parents were inbred and performed normally, and both sisters performed normally. The patient's parents were consanguineous and performed normally, and both sisters performed normally, consistent with autosomal recessive inheritance. Autoimmune polyendocrine syndrome (APS), also known as polyglandular autoimmune syndrome (PGA), refers to a series of syndromes in which the main manifestation is the impaired function of multiple endocrine glands caused by autoimmunity. It can also involve other non-endocrine gland tissues. APS I includes primary hypoadrenocorticism, hypoparathyroidism, and chronic mucocutaneous candidiasis, at least two of which are present, and can be associated with other related immune diseases, independent of HLA; APS II refers to primary hypoadrenocorticism with autoimmune thyroid disease and/or type 1 diabetes), and can be associated with other autoimmune diseases, but not with parathyroidism or candidiasis, associated with HLA; APS III refers to autoimmune thyroid disease with one or more autoimmune disorders, but not with hyperalgesia [1]. 1. The disease is rare: APS type I, also known as autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (Autoimmune polyendocrinopathy- candidosis-ectodermal dystrophy APECED) syndrome, is a rare autosomal recessive disorder. The cause of APS I is known to be completely different from other APS and is the only HLA-independent autoimmune disease caused by mutations in the autoimmune regulatory gene (AIRE) located at 21q22.3. The disease is distinctly race-specific, and the available case reports are mainly from Finns, Iranian Jews and Sardinians, with more than 200 cases reported so far, including 68 cases from 54 families in Finland [2], 71 cases from various ethnic groups in the United States and 41 cases in Italy, 23 cases from Iranian Jewish families, and 22 cases in Sardinia. All other ethnic groups were reported as individual cases, and the prevalence of APS I is presumed to be about 1 in 25,000 in the Finnish population, where the most cases were reported, and the disease is also unusually high in certain subgroups of Finns. The prevalence in the Iranian Jewish population is approximately 1:6,500 to 1:9,000, which is no less prevalent than in the Finnish population, where candidiasis is rare compared with the Finnish population. APS type I has not been reported in the Chinese population. We reviewed case reports of APS in China since 1980 [3-10], of which there were only three cases with two of the three, hypoparathyroidism and hypoadrenocorticism, and cutaneous mucocutaneous candidiasis, two from Guangzhou, and case 1 was a 37-year-old woman who presented with secondary amenorrhea for 3 years, dizziness, weakness, palpitations and wasting for 2 years, and hypocalcemic convulsions, diagnosed as hyperthyroidism The patient had no skin pigmentation, blood cortisol 0.6 mg/dl, 24-hour urinary 17-OHCS 1.2-2.6 mg/24h,4.1 mg/24h after ACTH excitation, therefore, hypoadrenocorticism was presumed to be secondary to anterior pituitary hypoplasia rather than adrenal self The second case from the same source was a 21-year-old female with primary amenorrhea, hepatitis B, type 1 diabetes mellitus for 2 years with ketoacidosis and hypocalcemic convulsions, diagnosed as diabetes mellitus, hypoparathyroidism and hypoadrenocorticism subclinical type, as the patient had no skin pigmentation and no adrenocortical function Since the patient had no skin pigmentation and no clinical manifestations of hypoadrenocorticism, and was discharged without glucocorticoid replacement therapy, the diagnosis of hypoadrenocorticism based only on low 17-OHCS (6.5 mg/24h) was not sufficient evidence to exclude the possibility of test error, at least not primary hypoadrenocorticism, so it did not belong to the APSI type either. In another case, reported from Nanjing in 1980 [3], the patient was a 40-year-old male who presented with darkening of the skin, lethargy, weakness, nausea and hypotension at the age of 28 and hypocalcemic convulsions at the age of 30. The diagnosis of hypoadrenocorticism with idiopathic hypoparathyroidism was consistent with the diagnosis of APS type I. The presence or absence of cutaneous mucosal Candida infection and the presence or absence of family history were not mentioned in this report. 2. Pathogenesis: Nagamine and the Finnish-German APECED Collaborative Group independently identified the causative gene of APECED, called AIRE (autoimmune regulator), in 1997 and hypothesized that its 1,635 bp open reading frame encodes 545 amino acids, with an isoelectric point of 7.32 and a molecular weight of 57,723, with 14 This gene is the first autoimmune gene found outside the MHC (on chromosome 6) and multiple mutations have been identified in patients [11]. The AIRE cDNA APECED protein was transiently expressed in COS-1, HeLa and NIH 3T3 cells, and immunohistochemical staining of transfected cells suggested that most of the recombinant 58-kD APECED protein appeared in the nucleus in a punctate form, and these structures did not overlap with nucleosomes [12].The AIRE protein is present in several human immune tissues, such as thymocyte subpopulations, spleen and lymph nodes and some blood mononuclear cells, among others. Immunological studies have detected multiple autoantibodies in some patients with APS-I, such as parathyroid autoantibodies, autoantibodies to extracellular sites of calcium-sensitive receptors, adrenocortical autoantibodies, autoantibodies to steroid-producing cells, autoantibodies to complement-fixed melanocytes, antibodies to transcription factors SOX9 and SOX10, [13] antibodies to mural cells and endogenous factors, antibodies to pancreatic islet cells and antibodies to glutamic acid decarboxylase, etc., presumably due to mutations in the AIRE gene that cause abnormal immune regulation pathogenesis through some mechanism. The clinical manifestations are complex and varied: in the available reports, the incidence is equal in men and women, mostly solitary, or sibling disease, and its clinical features are primary hypoadrenocorticism, hypoparathyroidism and chronic mucocutaneous candidiasis, generally two of the three syndromes exist, and can also be accompanied by other endocrine gland autoimmune diseases, (such as hypothyroidism and hypogonadism, type 1 diabetes, and hypopituitarism), and hypopituitarism. and hypopituitarism), autoimmune or immune-mediated gastrointestinal disorders (chronic atrophic gastritis, pernicious anemia, absorption disorders), chronic active hepatitis, autoimmune skin disorders (alopecia, vitiligo), ectodermal dysplasia (nail dystrophy, dental axial hypoplasia), myopathy, pure red lineage retrolisthesis, anosmia, keratoconus, cholelithiasis, tympanic membrane and vascular calcification[11] . The earliest onset is usually in early childhood, with the three main manifestations appearing successively before the age of 20 years, while other concomitant diseases may appear only at the age of 50 years, with the majority presenting first with candidiasis, usually before the age of 5 years, followed by hypoparathyroidism, at an average age of about 10 years, and then hyperaldosteronism, usually before the age of 15 years, although the three main manifestations appear in a certain order, but only Although the three main manifestations appear in a certain order, only 1/3-1/2 patients present with all three manifestations, and it has been reported that the earlier the first manifestation appears, the more likely it is to have multiple manifestations, and conversely the later the clinical manifestation appears, the more simple the clinical manifestation is. Since the clinical manifestations of APS1 are very complex, and some manifestations appear gradually with age, they should be followed up for life. Since cutaneous mucocutaneous candidiasis is mostly the earliest manifestation of APS1 and can be seen as its ultra-early marker, patients with cutaneous mucocutaneous candidiasis, especially in children, should all be carefully evaluated for immunological, biochemical and clinical follow-up to identify possible endocrine gland hypofunction. 4. Prognosis of the disease: Early reports of APS1 had a poor prognosis, with most deaths occurring before the age of 30 years; later series of studies have increased the survival rate, and of the 68 cases studied in Finland, 9 have died: 1 from adrenal crisis, 1 from diabetic ketoacidosis, 2 from fulminant liver failure, 1 from oral mucosal cancer, 1 from sudden death associated with hypoparathyroidism, 1 from sepsis, 1 from a traffic accident, and 1 from an unknown cause. Betterle reported 4 deaths, 1 at age 11 from fulminant liver failure, 1 at age 11 from systemic Candida infection due to immunosuppressive agents in hemolytic anemia, and 1 at age 36 from oral mucosal carcinoma. References: 1 Betterle C, Greggio N A, Volpato M. Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998,83: 1049-1055. 2 Ahonen P, Myllarniemi S, Sipila I.,et al. Clinical variation of autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. New Eng. J. Med. 1990. 322: 1829-1836. 3 Chen Pei-kwan. Report of two cases of multiple endocrine syndrome. Railway Medicine. 1980.4; (2): 68-69 4 Zheng Baiti, Hu Guoxian, Zhu Xixing, Zhong Xueli. Report of 5 cases of multiple hypoendocrine disorders. Chinese Journal of Internal Medicine 1981; (6): 342-346 5 Gao JD. Multiple endocrine adenopathies: report of one case of hyperthyroidism with hyperaldosteronism. Journal of Qinghai Medicine 1985.2; (1): 42-43 6 Wang H, Ma L, Cai WC. Thirty cases of multiple endocrinopathies with hypo- and hyperfunctional syndromes. Ningxia Medical Journal 2001; 23(2): 113 7 Liang YC. Report of 2 cases of multiple hypoendocrine disorders. New Medicine 1988; (6): 296 8 Yu Zulong. Twelve cases of multiple endocrine adenopathy. West China Medicine 1991; (3): 267-269 9 Lu Weiping; Yin Xiande; Zheng Linong. Four cases of multiple hypoendocrine disorders. Journal of Nanjing Medical University. 1995; 15(3): 73 10 Wang S.Z., Xie M.Z. Report of four cases of multiple hypoendocrine disorders. Journal of Practical Medicine 1985; (5): 23-25 11 Nithiyananthan, R, Heward J M, et al. A heterozygous deletion of the autoimmune regulator (AIRE1) gene, autoimmune thyroid disease, and type 1 diabetes: no evidence for association. J Clin Endocrinol Metab 2000;85: 1320-1322. 12 Bjorses P, Pelto-Huikko M, Kaukonen, et al. Localization of the APECED protein in distinct nuclear structures. Hum Molec Genet. 1999;8: 259-266. 13 Hedstrand H, Ekwall O, Olsson M, et, al. The transcription factors SOX9 and SOX10 are vitiligo autoantigens in autoimmune polyendocrine syndrome type I . J. Biol. Chem. 2001; 276: 35390-35395.