- Email: [email protected]
Nonclassic 21-hydroxylase deficiency
Nonclassic 21-hydroxylase deficiency Maria I. New, M.D. Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
Nonclassic 21-hydroxylase deficiency is a frequent autosomal recessive disorder which causes decreased fertility and is easily treated. It occurs with the highest frequency of any other autosomal recessive disorder in humans. (Fertil Steril威 2006;86(Suppl 1):S2. ©2006 by American Society for Reproductive Medicine.) Key Words: 21-hydroxylase deficiency, congenital adrenal hyperplasia, autosomal recessive disorders
We have discovered the most frequent genetic autosomal recessive disorder in humans, a mild form of congenital adrenal hyperplasia that we call “nonclassic 21-hydroxylase deficiency” (NC21OHD) (1, 2). This disorder causes symptoms (and other reproductive disorders) (1–3) including acne, short stature in both sexes (4, 5), hirsutism, and malepattern hair loss in women—all of which are reversible with proper diagnosis and treatment. The disorder has ethnic specificity: It is especially common in Ashkenazi (Eastern European) Jews, in whom 1 in 27 has the disorder and 1 in 3 is a carrier. It is also highly prevalent in persons of Hispanic (1:40), Slavic (1:50), and Italian (1:300) descent (6). In these groups, NC21OHD is more common than sickle cell anemia, Tay-Sachs, cystic fibrosis, or phenylketonuria, much better known diseases which are less amenable to treatment (6, 7). In contrast, we have found that treatment for NC21OHD reverses symptoms in as little three months. Treatment of affected children can improve their adult height (4, 5), eliminate acne during adolescence, and normalize puberty. Tragically, many children with NC21OHD are only identified after they have precocious puberty, stunted final height, or acne scars. Our group has conducted extensive research on this disorder. We identified and cloned the gene for 21OHD, deterReceived January 23, 2006; revised and accepted March 7, 2006. Supported in part by National Institutes of Health award HD 00072. Presented at the Third International Androgen Excess Society Meeting, Ravello, Italy, September 30 –October 1, 2005. Reprint requests: Maria I. New, M.D., Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, New York 10029.
S2
mining mutations specific to both the severe (“classic”) and nonclassic forms. We have introduced important new treatments for classic and nonclassic 21OHD, including prenatal treatment for classic 21OHD to prevent masculinization of the female genitalia (8). REFERENCES 1. Rumsby G, Avey CJ, Conway GS, Honour JW. Genotype-phenotype analysis in late onset 21-hydroxylase deficiency in comparison to the classical forms. Clin Endocrinol (Oxf) 1998;48:707–11. 2. Kohn B, Levine LS, Pollack MS, Pang S, Lorenzen F, Levy D, et al. Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia. J Clin Endocrinol Metab 1982;55:817– 827. 3. New M. Infertility and androgen excess in nonclassical 21-hydroxylase deficiency. In: Filicori M, Flamigni C, editors. The ovary: Regulation, dysfunction and treatment. Proceedings of the Symposium; 1996 January 25–27; New York: Excerpta Medica, 1996:195– 8. 4. Quintos J, Vogiatzi M, Harbison M, New M. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001;86:1511–7. 5. Lin-Su K, Vogiatzi MG, Marshall I, Harbison MD, Macapagal MC, Betensky B, et al. Treatment with growth hormone and luteinizing hormone releasing hormone analog improves final adult height in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2005;90:3318 –25. 6. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 1985;37:650 – 67. 7. Zerah M, Ueshiba H, Wood E, Speiser PW, Crawford C, McDonald T, et al. Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study. J Clin Endocrinol Metab 1990;70:1662–7. 8. New M, Carlson A, Obeid J, Marshall I, Cabrera M, Goseco A, et al. Extensive Personal Experience: prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. J Clin Endocrinol Metab 2001;86:5651–7.
Fertility and Sterility姞 Vol. 86, Suppl 1, July 2006 Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/06/$32.00 doi:10.1016/j.fertnstert.2006.03.005
Nonclassic 21-hydroxylase deficiency is a frequent autosomal recessive disorder which causes decreased fertility and is easily treated. It occurs with the highest frequency of any other autosomal recessive disorder in humans. (Fertil Steril威 2006;86(Suppl 1):S2. ©2006 by American Society for Reproductive Medicine.) Key Words: 21-hydroxylase deficiency, congenital adrenal hyperplasia, autosomal recessive disorders
We have discovered the most frequent genetic autosomal recessive disorder in humans, a mild form of congenital adrenal hyperplasia that we call “nonclassic 21-hydroxylase deficiency” (NC21OHD) (1, 2). This disorder causes symptoms (and other reproductive disorders) (1–3) including acne, short stature in both sexes (4, 5), hirsutism, and malepattern hair loss in women—all of which are reversible with proper diagnosis and treatment. The disorder has ethnic specificity: It is especially common in Ashkenazi (Eastern European) Jews, in whom 1 in 27 has the disorder and 1 in 3 is a carrier. It is also highly prevalent in persons of Hispanic (1:40), Slavic (1:50), and Italian (1:300) descent (6). In these groups, NC21OHD is more common than sickle cell anemia, Tay-Sachs, cystic fibrosis, or phenylketonuria, much better known diseases which are less amenable to treatment (6, 7). In contrast, we have found that treatment for NC21OHD reverses symptoms in as little three months. Treatment of affected children can improve their adult height (4, 5), eliminate acne during adolescence, and normalize puberty. Tragically, many children with NC21OHD are only identified after they have precocious puberty, stunted final height, or acne scars. Our group has conducted extensive research on this disorder. We identified and cloned the gene for 21OHD, deterReceived January 23, 2006; revised and accepted March 7, 2006. Supported in part by National Institutes of Health award HD 00072. Presented at the Third International Androgen Excess Society Meeting, Ravello, Italy, September 30 –October 1, 2005. Reprint requests: Maria I. New, M.D., Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, New York 10029.
S2
mining mutations specific to both the severe (“classic”) and nonclassic forms. We have introduced important new treatments for classic and nonclassic 21OHD, including prenatal treatment for classic 21OHD to prevent masculinization of the female genitalia (8). REFERENCES 1. Rumsby G, Avey CJ, Conway GS, Honour JW. Genotype-phenotype analysis in late onset 21-hydroxylase deficiency in comparison to the classical forms. Clin Endocrinol (Oxf) 1998;48:707–11. 2. Kohn B, Levine LS, Pollack MS, Pang S, Lorenzen F, Levy D, et al. Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia. J Clin Endocrinol Metab 1982;55:817– 827. 3. New M. Infertility and androgen excess in nonclassical 21-hydroxylase deficiency. In: Filicori M, Flamigni C, editors. The ovary: Regulation, dysfunction and treatment. Proceedings of the Symposium; 1996 January 25–27; New York: Excerpta Medica, 1996:195– 8. 4. Quintos J, Vogiatzi M, Harbison M, New M. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001;86:1511–7. 5. Lin-Su K, Vogiatzi MG, Marshall I, Harbison MD, Macapagal MC, Betensky B, et al. Treatment with growth hormone and luteinizing hormone releasing hormone analog improves final adult height in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2005;90:3318 –25. 6. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 1985;37:650 – 67. 7. Zerah M, Ueshiba H, Wood E, Speiser PW, Crawford C, McDonald T, et al. Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study. J Clin Endocrinol Metab 1990;70:1662–7. 8. New M, Carlson A, Obeid J, Marshall I, Cabrera M, Goseco A, et al. Extensive Personal Experience: prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. J Clin Endocrinol Metab 2001;86:5651–7.
Fertility and Sterility姞 Vol. 86, Suppl 1, July 2006 Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/06/$32.00 doi:10.1016/j.fertnstert.2006.03.005