{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:02Z","timestamp":1784557022367,"version":"3.55.0"},"reference-count":56,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2018,10,13]],"date-time":"2018-10-13T00:00:00Z","timestamp":1539388800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/deed.en_GB"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,13]]},"abstract":"Summary<\/jats:title>\n Congenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3\u03b2-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3\u03b2-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3\u03b2-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY\/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well.<\/jats:p>\n \n Learning points:<\/jats:title>\n \n \n Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH.<\/jats:p>\n <\/jats:list-item>\n \n High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3\u03b2-HSD enzyme deficiency.<\/jats:p>\n <\/jats:list-item>\n \n \n Final diagnosis can be obtained with sequencing of\n HSD3B2<\/jats:italic>\n gene showing various mutations.\n <\/jats:p>\n <\/jats:list-item>\n \n Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism.<\/jats:p>\n <\/jats:list-item>\n \n Karyotyping in such patient may rarely show mosaic KS (47,XXY\/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-18-0108","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T10:31:14Z","timestamp":1539599474000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":5,"title":["A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity"],"prefix":"10.1530","volume":"2018","author":[{"given":"M A","family":"Shehab","sequence":"first","affiliation":[{"name":"1Department of Endocrinology, BSMMU, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahseen","family":"Mahmood","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, BSMMU, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Hasanat","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, BSMMU, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md","family":"Fariduddin","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, BSMMU, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazmul","family":"Ahsan","sequence":"additional","affiliation":[{"name":"2Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Shahnoor","family":"Hossain","sequence":"additional","affiliation":[{"name":"2Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Shahdat","family":"Hossain","sequence":"additional","affiliation":[{"name":"2Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmin","family":"Jahan","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, BSMMU, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref41","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ejmg.2005.09.001","article-title":"Rare XXY\/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report","volume":"49","year":"2006","journal-title":"European Journal of Medical Genetics"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0022-2836(75)90213-2","article-title":"A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase","volume":"94","year":"1975","journal-title":"Journal of Molecular Biology"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1469-7610.1978.tb00465.x","article-title":"A method for longitudinal study of behavioral development in infants and children: the early development of XXY children","volume":"19","year":"1978","journal-title":"Journal of Child Psychology and Psychiatry"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13052-018-0485-x","article-title":"A Klinefelter boy with congenital adrenal hyperplasia: too much or too little androgens?","volume":"44","year":"2018","journal-title":"Italian Journal of Pediatrics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0889-8529(08)70020-3","article-title":"Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency","volume":"30","year":"2001","journal-title":"Endocrinology Metabolism Clinics of North America"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1210\/jc.2007-2417","article-title":"Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4103\/1008-682X.122201","article-title":"The role of hypogonadism in Klinefelter syndrome","volume":"16","year":"2014","journal-title":"Asian Journal of Andrology"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13052-018-0485-x","article-title":"A Klinefelter boy with congenital adrenal hyperplasia: too much or too little androgens?","volume":"44","year":"2018","journal-title":"Italian Journal of Pediatrics"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1210\/er.2002-0050","article-title":"Molecular biology of the 3beta-hydroxysteroid dehydrogenase\/delta5-delta4 isomerase gene family","volume":"26","year":"2005","journal-title":"Endocrine Reviews"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"20150113","DOI":"10.1098\/rstb.2015.0113","article-title":"The importance of having two X chromosomes","volume":"371","year":"2016","journal-title":"Philosophical Transactions of the Royal Society of London: Series B, Biological Sciences"},{"key":"ref71","first-page":"1012","article-title":"Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3\u03b2-hydroxysteroid dehydrogenase deficiency","volume":"79","year":"1994","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/14.4.946","article-title":"Klinefelter\u2019s syndrome in the male infertility clinic","volume":"14","year":"1999","journal-title":"Human Reproduction"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","article-title":"Klinefelter\u2019s syndrome","volume":"364","year":"2004","journal-title":"Lancet"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"201196","DOI":"10.1210\/jc.2010-2103","article-title":"of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome : insulin - like peptide levels are normal and positively correlated with LH levels of and https org","journal-title":"Assessment Journal Clinical Endocrinology Metabolism"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","article-title":"Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism","volume":"40","year":"2017","journal-title":"Journal of Endocrinological Investigation"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2164\/jandrol.107.004648","article-title":"21Hydroxylase deficiency and case report Klinefelter syndrome in an adult man: striking a balance between androgen excess and insufficiency.","volume":"29","year":"2008","journal-title":"Journal of Andrology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","article-title":"Klinefelter\u2019s syndrome","volume":"364","year":"2004","journal-title":"Lancet"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/ccr3.742","article-title":"Premature pubarche in a child with abnormal 3\u03b2\u2010hydroxysteroid dehydrogenase function and Klinefelter syndrome: the intriguing relationship between androgen deficiency and excess","volume":"5","year":"2017","journal-title":"Clinical Case Reports"},{"key":"ref231","first-page":"348","article-title":"Congenital adrenal hyperplasia with 47, XXY Klinefelter syndrome","volume":"102","year":"1994","journal-title":"Experimental and Clinical Endocrinology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.metabol.2017.09.017","article-title":"Klinefelter syndrome: more than hypogonadism","volume":"86","year":"2018","journal-title":"Metabolism Clinical and Experimental"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1677\/jme.0.0120225","article-title":"Mutation in the human gene for 3\u03b2-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss","volume":"12","year":"1994","journal-title":"Journal of Molecular Endocrinology"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/14.4.946","article-title":"Klinefelter\u2019s syndrome in the male infertility clinic","volume":"14","year":"1999","journal-title":"Human Reproduction"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.fertnstert.2013.12.051","article-title":"Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients","volume":"101","year":"2014","journal-title":"Fertility and Sterility"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1001\/archinte.158.12.1309","article-title":"Klinefelter syndrome","volume":"158","year":"1998","journal-title":"Archive of Internal Medicine"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1210\/jc.2007-2417","article-title":"Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.fertnstert.2013.12.051","article-title":"Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients","volume":"101","year":"2014","journal-title":"Fertility and Sterility"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1002\/ajmg.a.31408","article-title":"Maternal 21 hydroxylase deficiency and uniparentalisodisomy of chromosome 6 and X results in a child with 21-hydroxylase deficiency and Klinefelter syndrome","volume":"140A","year":"2006","journal-title":"American Journal of Medical Genetics Part A"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1002\/ajmg.a.31408","article-title":"Maternal 21 hydroxylase deficiency and uniparentalisodisomy of chromosome 6 and X results in a child with 21-hydroxylase deficiency and Klinefelter syndrome","volume":"140A","year":"2006","journal-title":"American Journal of Medical Genetics Part A"},{"key":"ref511","first-page":"348","article-title":"Congenital adrenal hyperplasia with 47, XXY Klinefelter syndrome","volume":"102","year":"1994","journal-title":"Experimental and Clinical Endocrinology"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0022-3476(72)80586-9","article-title":"The XXY (Klinefelter\u2019s) syndrome in childhood: detection and treatment","volume":"80","year":"1972","journal-title":"Journal of Pediatrics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1210\/jcem-2-11-615","article-title":"Syndrome characterized by gynecomastia, aspermatogenesis without a Leydigism and increased excretion of follicle-stimulating hormone","volume":"2","year":"1942","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref481","first-page":"225","article-title":"Summary of clinical findings in children and young adults with sex chromosome anomalies","year":"1991","journal-title":"Children and Young Adults with Sex Chromosome Aneuploidy Birth Defects: Original Article Series"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"20150113","DOI":"10.1098\/rstb.2015.0113","article-title":"The importance of having two X chromosomes","volume":"371","year":"2016","journal-title":"Philosophical Transactions of the Royal Society of London: Series B, Biological Sciences"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0022-3476(72)80586-9","article-title":"The XXY (Klinefelter\u2019s) syndrome in childhood: detection and treatment","volume":"80","year":"1972","journal-title":"Journal of Pediatrics"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1677\/jme.0.0120225","article-title":"Mutation in the human gene for 3\u03b2-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss","volume":"12","year":"1994","journal-title":"Journal of Molecular Endocrinology"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000106375","article-title":"Genital anomalies in Klinefelter\u2019s syndrome","volume":"68","year":"2007","journal-title":"Hormone Research in Paediatrics"},{"key":"ref201","first-page":"225","article-title":"Summary of clinical findings in children and young adults with sex chromosome anomalies","year":"1991","journal-title":"Children and Young Adults with Sex Chromosome Aneuploidy Birth Defects: Original Article Series"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1469-7610.1978.tb00465.x","article-title":"A method for longitudinal study of behavioral development in infants and children: the early development of XXY children","volume":"19","year":"1978","journal-title":"Journal of Child Psychology and Psychiatry"},{"key":"ref371","first-page":"893","year":"2016","journal-title":"Williams Textbook of Endocrinology"},{"key":"ref451","doi-asserted-by":"publisher","first-page":"201196","DOI":"10.1210\/jc.2010-2103","article-title":"of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome : insulin - like peptide levels are normal and positively correlated with LH levels of and https org","journal-title":"Assessment Journal Clinical Endocrinology Metabolism"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000106375","article-title":"Genital anomalies in Klinefelter\u2019s syndrome","volume":"68","year":"2007","journal-title":"Hormone Research in Paediatrics"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ejmg.2005.09.001","article-title":"Rare XXY\/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report","volume":"49","year":"2006","journal-title":"European Journal of Medical Genetics"},{"key":"ref341","first-page":"1678","article-title":"Characterization of two novel homozygous missense mutations involving codon 6 and 259 of type II 3\u03b2-hydroxysteroid dehydrogenase (3\u03b2HSD) gene causing, respectively, nonsalt-wasting and salt-wasting 3\u03b2HSD deficiency disorder","volume":"85","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref61","first-page":"1678","article-title":"Characterization of two novel homozygous missense mutations involving codon 6 and 259 of type II 3\u03b2-hydroxysteroid dehydrogenase (3\u03b2HSD) gene causing, respectively, nonsalt-wasting and salt-wasting 3\u03b2HSD deficiency disorder","volume":"85","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","article-title":"Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism","volume":"40","year":"2017","journal-title":"Journal of Endocrinological Investigation"},{"key":"ref91","first-page":"893","year":"2016","journal-title":"Williams Textbook of Endocrinology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1210\/er.2002-0050","article-title":"Molecular biology of the 3beta-hydroxysteroid dehydrogenase\/delta5-delta4 isomerase gene family","volume":"26","year":"2005","journal-title":"Endocrine Reviews"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4103\/1008-682X.122201","article-title":"The role of hypogonadism in Klinefelter syndrome","volume":"16","year":"2014","journal-title":"Asian Journal of Andrology"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1210\/jcem-2-11-615","article-title":"Syndrome characterized by gynecomastia, aspermatogenesis without a Leydigism and increased excretion of follicle-stimulating hormone","volume":"2","year":"1942","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0889-8529(08)70020-3","article-title":"Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency","volume":"30","year":"2001","journal-title":"Endocrinology Metabolism Clinics of North America"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/ccr3.742","article-title":"Premature pubarche in a child with abnormal 3\u03b2\u2010hydroxysteroid dehydrogenase function and Klinefelter syndrome: the intriguing relationship between androgen deficiency and excess","volume":"5","year":"2017","journal-title":"Clinical Case Reports"},{"key":"ref351","first-page":"1012","article-title":"Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3\u03b2-hydroxysteroid dehydrogenase deficiency","volume":"79","year":"1994","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.metabol.2017.09.017","article-title":"Klinefelter syndrome: more than hypogonadism","volume":"86","year":"2018","journal-title":"Metabolism Clinical and Experimental"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2164\/jandrol.107.004648","article-title":"21Hydroxylase deficiency and case report Klinefelter syndrome in an adult man: striking a balance between androgen excess and insufficiency.","volume":"29","year":"2008","journal-title":"Journal of Andrology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1001\/archinte.158.12.1309","article-title":"Klinefelter syndrome","volume":"158","year":"1998","journal-title":"Archive of Internal Medicine"},{"key":"ref551","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0022-2836(75)90213-2","article-title":"A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase","volume":"94","year":"1975","journal-title":"Journal of Molecular Biology"}],"container-title":["Endocrinology, Diabetes & Metabolism Case 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