Home Print this page Email this page Users Online: 98
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2016  |  Volume : 4  |  Issue : 1  |  Page : 37-39

A case of autoimmune polyendocrine syndrome type 1 with ocular findings and unique AIRE gene defect

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 Submission03-Jun-2014
Date of Acceptance04-May-2015
Date of Web Publication19-Jan-2016

Correspondence Address:
Handan Akil
Ophtalmology Clinic, Gorele State Hospital, 28800, Gorele, Giresun
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2320-3897.174414

Rights and Permissions

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 2022 Jul 4];4:37-9. Available from: https://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. [1] 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). [2] Nonendocrine disorders are ectodermal dystrophy, vitiligo, alopecia, pernicious anemia, chronic atrophic gastritis, malabsorption, and chronic active hepatitis. [2] The disabling ocular manifestations of the disease include chronic persistent keratoconjunctivitis, dry eye, iridocyclitis, retinal detachment, optic atrophy, cataract, and rarely retinitis pigmentosa. [3] APS 1 is caused by several mutations in the autoimmune regulator (AIRE) gene on chromosome 21 (21q22.3). [4]

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 Top

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].
Figure 1: Local alopecia

Click here to view
Figure 2: Bilateral loss of eyelashes and eyebrows

Click here to view
Figure 3: Dystrophy of the nails

Click here to view

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.
Figure 4: Posterior polar cataract

Click here to view
Figure 5: Retina pigment epithelium changes

Click here to view
Figure 6: Window defects of the fundus angiography

Click here to view

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].
Table 1: Diyagram of AIRE gene mutation

Click here to view

This mutation has not been previously reported.

  Discussion Top

APS 1 is an autoimmune disease that typically presents with candidiasis, hypoparathyroidism, and adrenocortical failure. [2],[5] The first symptoms usually appear in childhood, although the age of onset and the clinical phenotype vary widely, even within the same family. [1],[2]

APS1 has been described to have a well-established association with keratoconjunctivitis for a long time. [3],[6] Dry eye, retinal detachment, retinitis pigmentosa, optic atrophy, and rarely cataract can also occur with the disease. [3]

Merenmies and Tarkkanen reported that 17 of 69 patients with APS1 (25%) had bilateral keratitis. [6] 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. [6]

Chang et al., reported ophthalmic features in a series of 17 patients with APS1. [3] 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. [3] 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). [7]

Two cases with APS1 were reported to have retinitis pigmentosa. [8],[9] 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. [10]

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. [5]

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.

  References Top

Betterle C, Greggio NA, Volpato M. Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998;83:1049-55.  Back to cited text no. 1
Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990;322:1829-36.  Back to cited text no. 2
Chang B, Brosnahan D, McCreery K, Dominguez M, Costigan C. Ocular complucation of autoimmune poliendocrinopathy syndrome type 1. J AAPOS 2006;10:515-20.  Back to cited text no. 3
Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nat Genet 1997;17:393-8.  Back to cited text no. 4
Meloni A, Perniola R, Faa V, Corvaglia E, Cao A, Rosatelli MC. Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy patients from southern Italy. J Clin Endocrinol Metab 2002;87:841-6.  Back to cited text no. 5
Merenmies L, Tarkkanen A. Chronic bilateral keratitis in autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy (APECED). A long term follow-up and visual prognosis. Acta Opthalmol Scand 2000;78:532-5.  Back to cited text no. 6
Rajendram R, Deane JA, Barnes M, Swift PG, Adamson K, Pearce S, et al. Rapid onset childhood cataracts leading to the diagnosis of autoimmune polyendocrinopathy- candidiasis- ectodermal dystrophy. Am J Ophthalmol 2003;136:951-2.  Back to cited text no. 7
Gass JD. The syndrome of keratoconjunctivitis, superficial moniliasis, idiopathic hypoparathyroidism and Addison's disease. Am J Ophthalmol 1962;54:660-74.  Back to cited text no. 8
Wood LW, Jampol LM, Daily MJ. Retinal and optic nerve manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Arch Ophthalmol 1991;109:1065.  Back to cited text no. 9
Vogel A, Strassburg CP, Obermayer-Straub P, Brabant G, Mann MP. The genetic background of autoimmune plyendocrinopathy-candidiasis-ectodermal dystrophy and its autoimmune disease components. J Mol Med 2002;80:201-11.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

This article has been cited by
1 Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature
Dhruvkumar M. Patel,Jayanti K. Gurumikhani,Mukundkumar V. Patel,Maitri M. Patel,Suyog Y. Patel,Prathna N. Patel
Current Drug Safety. 2021; 16(1): 101
[Pubmed] | [DOI]
2 APECED in Turkey: A case report and insights on genetic and phenotypic variability
Alessandra Fierabracci,Marsha Pellegrino,Federica Frasca,Sara Sebnem Kilic,Corrado Betterle
Clinical Immunology. 2018; 194: 60
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Report
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded215    
    Comments [Add]    
    Cited by others 2    

Recommend this journal