Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Case Report Med Princ Pract 2009;18:482–485 DOI: 10.1159/000235899 49,XXXXY Syndrome with Autoimmune Diabetes and Ocular Manifestations Baris Onder Pamuk a Ayse Nur Torun a Mustafa Kulaksizoglu a Cengiz Algan b Derun Taner Ertugrul a Zerrin Yilmaz c Neslihan Bascil Tutuncu a Nilgun Guvener Demirag a Departments of a Endocrinology and Metabolism, b Ophthalmology and c Medical Genetics, Faculty of Medicine, Baskent University, Ankara, Turkey Introduction First described by Fraccaro et al. [1], 49,XXXXY syn- drome is a rare disorder with an incidence of 1 in 85,000 male births. The classical phenotype of this syndrome includes mental retardation, radioulnar synostosis and hypogonadism [2]. In 1942, Klinefelter et al. [3] described a syndrome in which postpubertal males demonstrated tall stature, infertility, gynecomastia and lack of pubertal virilization, testicular failure, azoospermia, elevated go- nadotropin levels and decreased 17-ketosteroid levels, but it was not until 1959 that Jacobs and Strong [4] confirmed that these males had a chromosomal disorder with an ex- tra X chromosome. Males with more than 1 extra sex chromosome (e.g. 48,XXYY, 48,XXXY, 49,XXXXY) are diagnosed with Klinefelter syndrome variants. They are not common, and have distinctive physical and behav- ioral features. Klinefelter syndrome has come to encom- pass the variants as well as the more common 47,XXY chromosome variation. Patients with 49,XXXXY syn- drome have a distinct appearance, including characteris- tic facial features, cardiac defects, multiple skeletal anom- alies, abnormalities of the genitalia, mental deficiency and speech problems, which have not been reported in Klinefelter syndrome patients [2] . In this report, we pre- sent a rare case of pentasomy 49,XXXXY complicated Key Words 49,XXXXY syndrome  Autoimmune diabetes  Cataract  Glaucoma Abstract Objective: We report a rare case of 49,XXXXY syndrome with autoimmune diabetes (requiring insulin therapy), bilateral cataracts and unilateral glaucoma. Clinical Presentation and Intervention: A 25-year-old man with mental retarda- tion presented with multiple skeletal abnormalities, polyuria and polydipsia. He had high glucose concentrations, with- out ketonuria, and hypergonadotropic hypogonadism. Oph- thalmic examination revealed a polar cataract in both eyes and increased intraocular pressure in the left eye. The anti- islet cell antibody test was positive, and anti-glutamic acid decarboxylase autoantibody levels were elevated. Karyo- type analysis revealed 49,XXXXY. Intensive insulin therapy and testosterone replacements were started. Conclusion: The autoimmune nature of diabetes that we observed in our patient seems to be predisposed by hypogonadism. Cata- ract and glaucoma in this case seem to be the result of dia- betes, and an association of these ocular manifestations with the syndrome 49,XXXXY seems unlikely. Copyright © 2009 S. Karger AG, Basel Received: August 25, 2008 Revised: February 5, 2009 Baris Onder Pamuk Department of Endocrinology and Metabolic Disease Faculty of Medicine, Baskent University, 5th Street No: 48, Bahcelievler TR–06490 Ankara (Turkey) Tel. +90 312 212 2912, Fax +90 312 215 4216, E-Mail bopamuk@yahoo.com © 2009 S. Karger AG, Basel 1011–7571/09/0186–0482$26.00/0 Accessible online at: www.karger.com/mpp