|Year : 2016 | Volume
| Issue : 1 | Page : 37-39
A case of autoimmune polyendocrine syndrome type 1 with ocular findings and unique AIRE gene defect
Handan Akil1, Ayse Derya Bulus2, Nesibe Andiran2, Pascale Saugier Veber3, Soner Keskin4
1 Ophtalmology Clinic, Gorele State Hospital, Giresun, Turkey
2 Pediatric Endocrinology Clinic, Kecioren Training and Research Hospital, Ankara, Turkey
3 Molecular Genetic Laboratory, Department of Genetics, Rouen Faculty of Medicine, Rouen, France
4 Ophtalmology Clinic, Aydin State Hospital, Aydin, Turkey
|Date of Submission||03-Jun-2014|
|Date of Acceptance||04-May-2015|
|Date of Web Publication||19-Jan-2016|
Ophtalmology Clinic, Gorele State Hospital, 28800, Gorele, Giresun
Source of Support: None, Conflict of Interest: None
Autoimmune polyendocrine syndrome type 1 (APS 1) is a rare autosomal recessive disorder that is characterized by autoimmunity against endocrine and ectodermal tissues. Clinical manifestations usually appear in childhood and consist of hypoparathyroidism, oral candidiasis, and adrenocortical insufficiency. Ocular complications include keratoconjunctivitis, dry eye, iridocyclitis, cataract, retinitis pigmentosa, and optic atrophy.
We report a 9-year-old girl with APS 1 who had polar cataract in her left eye (LE), retinal changes with retinal pigment atrophy, and a new autoimmune regulator (AIRE) gene defect on chromosome 21. When a pediatric patient presents with decreased visual acuity with a history of chronic mucocutaneous candidiasis, ectodermal dysplasias, or hypoparathyroidism, we should consider the diagnosis of APS type 1 and arrange a pediatric endocrinological evaluation. The gene studied in this case may contribute to the characterization of the molecular pathology of the AIRE gene and may allow preclinical diagnosis in families at risk.
Keywords: AIRE gene mutation, autoimmune polyendocrine syndrome, cataract
|How to cite this article:|
Akil H, Bulus AD, Andiran N, Veber PS, Keskin S. A case of autoimmune polyendocrine syndrome type 1 with ocular findings and unique AIRE gene defect. J Clin Ophthalmol Res 2016;4:37-9
|How to cite this URL:|
Akil H, Bulus AD, Andiran N, Veber PS, Keskin S. A case of autoimmune polyendocrine syndrome type 1 with ocular findings and unique AIRE gene defect. J Clin Ophthalmol Res [serial online] 2016 [cited 2019 Feb 20];4:37-9. Available from: http://www.jcor.in/text.asp?2016/4/1/37/174414
Autoimmune polyendocrine syndrome type 1 (APS1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autosomal recessive disorder.  The clinical diagnosis is based on the presence of two of the three commonest clinical manifestations that are chronic mucocutaneous candidiasis, primary hypoparathyroidism, and primary adrenocortical insufficiency (Addison's disease).  Nonendocrine disorders are ectodermal dystrophy, vitiligo, alopecia, pernicious anemia, chronic atrophic gastritis, malabsorption, and chronic active hepatitis.  The disabling ocular manifestations of the disease include chronic persistent keratoconjunctivitis, dry eye, iridocyclitis, retinal detachment, optic atrophy, cataract, and rarely retinitis pigmentosa.  APS 1 is caused by several mutations in the autoimmune regulator (AIRE) gene on chromosome 21 (21q22.3). 
Here we report a novel AIRE gene mutation in a patient with rare ocular findings and symptoms of hypoparathyroidism, mucocutaneous candidiasis, ectodermal dysplasia, and pernicious anemia.
| Case Report|| |
A 9-year-old female was admitted in the hospital because of alopecia. She had multiple minimal local alopecia and bilateral loss of eyelashes and eyebrows [Figure 1] and [Figure 2]. She had oral candidiasis and ectodermal dysplasia and ectodermal dystrophy of nails, but did not have vitiligo [Figure 3].
The patient was the first child of first-degree consanguineously married Turkish parents. The pregnancy and birth were uneventful. There was nothing significant in the family history.
In history, it was learned that 1 year ago, she was admitted to another hospital for lethargy and convulsions. The diagnosis of hypoparathyroidism was made and subsequently, she was put on calcitriol and calcium therapy. There was history of intractable diaper dermatitis and recurrent oral candidiasis during her infancy.
The patient's laboratory examination at presentation: Serum calcium: 9.1 (9-10.8) mg/dl, phosphate: 6.3 (4.5-5.5) mg/dl, parathyroid hormone: 1.2 (11-75)pg/ml, glucose: 94 (70-100) mg/dl, renal, hepatic functions, and electrolytes were normal. She was diagnosed as megaloblastic anemia with vitamin B12 level: 34 (126.5-505) pg/ml, hemoglobin:11.6 g/dl, and mean corpuscular volume (MCV):102.3 Fl. Thyroid and adrenal gland function tests were normal. Upper endoscopy, performed for pernicious anemia, demonstrated endoscopic and histological evidence of gastric atrophy.
She was seen in ophthalmology department due to complaint of blurred vision. Her best corrected visual acuity was 20/50 right eye (RE) and 20/50 left eye (LE). Intraocular pressures were normal (12 mmHg RE and 14 mmHg LE). Slit-lamp examination showed a posterior polar cataract in the LE [Figure 4]. On ophthalmoscopic examination, there was a vitreous degeneration at RE and bilateral atrophy of macular retinal pigment epithelium, peripapillary hyperpigmentation, and diffuse hypo-hyperpigmented areas [Figure 5]. Her fundus angiography demonstrated window defects consistent with the atrophic areas of retinal pigment epithelium [Figure 6]. Surgery was planned for cataract. Calcium and calcitriol treatment was continued.
For determination of AIRE gene mutation, genetic analysis was performed. Blood samples were obtained after written informed consent from the parents. The screening of the entire coding regions of the AIRE gene in patient's DNA led to the identification of a homozygous 9 bp deletion in exon 2 removing three amino acids: C.267-275del (p.Tyr90-Arg92del) [Table 1].
This mutation has not been previously reported.
| Discussion|| |
APS 1 is an autoimmune disease that typically presents with candidiasis, hypoparathyroidism, and adrenocortical failure. , The first symptoms usually appear in childhood, although the age of onset and the clinical phenotype vary widely, even within the same family. ,
APS1 has been described to have a well-established association with keratoconjunctivitis for a long time. , Dry eye, retinal detachment, retinitis pigmentosa, optic atrophy, and rarely cataract can also occur with the disease. 
Merenmies and Tarkkanen reported that 17 of 69 patients with APS1 (25%) had bilateral keratitis.  The first presenting symptom of their 12 patients was chronic mucocutaneous candidiasis like our patient. Among them 12 patients had cortical opacities, which could be attributed to the patients' hypoparathyroidism. 
Chang et al., reported ophthalmic features in a series of 17 patients with APS1.  Three of 17 (18%)patients had lens opacities, none of which appeared to affect visual acuity. One of the female patients with lens opacities was 15 years of age. She had a unilateral small posterior polar cataract. This patient also had alopecia and loss of eyelashes and eyebrows. Our patient who was also a female, had similar clinical findings. The only difference was that she was affected with visual impairment. The other patient in Chang et al., series with lens opacity was a 14-year-old male patient who had dot opacities in his lenses, and had alopecia and the loss of eyelashes and eyebrow. Three of them had cortical cataracts.  Rajendram et al., reported a 12-year-old boy who developed progressive bilateral cataracts that reduced his visual acuity to 20/200, which was thought to be associated with previous hypocalcemia. He later developed adrenocortical failure and other findings of APS1 (alopecia, skin and nail changes, and insulin dependent diabetes). 
Two cases with APS1 were reported to have retinitis pigmentosa. , Our patient had retinal pigmentary changes with pigment epithelial atrophy. Family history of inherited retinal abnormalities was however negative. Since APS1 is an autoimmune syndrome, we hypothesized that atrophy of the retina in the presence of autoantibodies directed against these tissues suggests that retinal findings are autoimmune and part of the syndrome.
The mutated AIRE gene results in defective AIRE proteins which cause autoimmune destruction of target organs by disturbing the immunological tolerance of the patients. In the coding region of the AIRE gene, approximately 60 different mutations have been reported. 
The mutation c.267-275del (p.Tyr90-Arg92del) described in our patient has not been reported in the literature before according to best of our knowledge. The identification of this homozygous mutation in exon2 of the AIRE gene (c.267-275del (p.Tyr90-Arg92del)) allows the confirmation on molecular basis of the diagnosis of APS1 in patient. The 9 bp-deletion (c.267_275del; p.Tyr90_Arg92del) removes three aminoacids. A missense mutation involving the codon at the same position 90 has been described (c.269A>G;p.Tyr90Cys) giving evidence that this codon is crucial for the function of the protein. 
In conclusion; when a pediatric patient presents with decreased visual acuity with a history of chronic mucocutaneous candidiasis, ectodermal dysplasias, or hypoparathyroidism; we should consider the diagnosis of APS1 and confirm the presence of this unique AIRE gene mutation on molecular basis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]