본문 바로가기
KERD
논문KCI 등재

Clinical and molecular review of atypical congenital adrenal hyperplasia

2

조회

0

다운로드

5

인용

0

참고문헌

키워드

주제분류소아과학

초록

Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the mutations in the genes encoding for steroidogenic enzymes that involved cortisol synthesis. More than 90% of cases are caused by a defect in the enzyme 21-hydroxylase. Four other enzyme deficiencies (cholesterol side-chain cleavage, 17α-hydroxylase [P450c17], 11β-hydroxylase [P450c11β], 3β-hydroxysteroid dehydrogenase) in the steroid biosynthesis pathway, along with one cholesterol transport protein defect (steroidogenic acute regulatory protein), and one electrontransfer protein (P450 oxidoreductase) account for the remaining cases. The clinical symptoms of the different forms of CAH result from the particular hormones that are deficient and those that are produced in excess. A characteristic feature of CAH is genital ambiguity or disordered sex development, and most variants are associated with glucocorticoid deficiency. However, in the rare forms of CAH other than 21-hydroxylase deficiency so-called “atypical CAH”, the clinical and hormonal phenotypes can be more complicated, and are not well recognized. This review will focus on the atypical forms of CAH, including the genetic analyses, and phenotypic correlates.

Abstract

Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the mutations in the genes encoding for steroidogenic enzymes that involved cortisol synthesis. More than 90% of cases are caused by a defect in the enzyme 21-hydroxylase. Four other enzyme deficiencies (cholesterol side-chain cleavage, 17α-hydroxylase [P450c17], 11β-hydroxylase [P450c11β], 3β-hydroxysteroid dehydrogenase) in the steroid biosynthesis pathway, along with one cholesterol transport protein defect (steroidogenic acute regulatory protein), and one electrontransfer protein (P450 oxidoreductase) account for the remaining cases. The clinical symptoms of the different forms of CAH result from the particular hormones that are deficient and those that are produced in excess. A characteristic feature of CAH is genital ambiguity or disordered sex development, and most variants are associated with glucocorticoid deficiency. However, in the rare forms of CAH other than 21-hydroxylase deficiency so-called “atypical CAH”, the clinical and hormonal phenotypes can be more complicated, and are not well recognized. This review will focus on the atypical forms of CAH, including the genetic analyses, and phenotypic correlates.

참고문헌 (56)

  1. Miller WL, "The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders", Endocr Rev, 32, pp.81~151 (2011)
  2. Suzuki T, "Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex: immunohistochemical studies", Clin Endocrinol (Oxf), 53, pp.739~747 (2000)
  3. Miller WL., "Minireview: regulation of steroidogenesis by electron transfer", Endocrinology, 146, pp.2544~2550 (2005)
  4. Stocco DM, "Regulation of the acute production of steroids in steroidogenic cells", Endocr Rev, 17, pp.221~244 (1996)
  5. Janejai N, "Congenital adrenal hyperplasia: should nationwide screening be implemented in Thailand?", Southeast Asian J Trop Med Public Health, 34(Suppl 3), pp.170~173 (2003)
  6. Somboonnithiphol K, "Newborn screening for congenital adrenal hyperplasia in Srinagarind Hospital, Khon Kaen University", Thailand. Asian Biomed, 5, pp.855~859 (2011), Khon Kaen University
  7. Lin D, "Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis", Science, 267, pp.1828~1831 (1995)
  8. Bose HS, "International Congenital Lipoid Adrenal Hyperplasia Consortium. The pathophysiology and genetics of congenital lipoid adrenal hyperplasia", N Engl J Med, 335, pp.1870~1878 (1996)
  9. Bose HS, "The active form of the steroidogenic acute regulatory protein, StAR, appears to be a molten globule", Proc Natl Acad Sci U S A, 96, pp.7250~7255 (1999)
  10. Tajima T, "Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency", J Clin Endocrinol Metab, 86, pp.3820~3825 (2001)
  11. Katsumata N, "Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A)cause congenital adrenal insufficiency in humans", J Clin Endocrinol Metab, 87, pp.3808~3813 (2002)
  12. Hiort O, "Homozygous disruption of P450 sidechain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure", J Clin Endocrinol Metab, 90, pp.538~541 (2005)
  13. al Kandari H, "Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum", J Clin Endocrinol Metab, 91, pp.2821~2826 (2006)
  14. Kim CJ, "Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc", J Clin Endocrinol Metab, 93, pp.696~702 (2008)
  15. Rubtsov P, "A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal insufficiency and hypospadias in a 46,XY patient", J Clin Endocrinol Metab, 94, pp.936~939 (2009)
  16. Sahakitrungruang T, "Partial defect in the cholesterol side-chain cleavage enzyme P450scc (CYP11A1) resembling nonclassic congenital lipoid adrenal hyperplasia", J Clin Endocrinol Metab, 96, pp.792~798 (2011)
  17. Tee MK, "Varied clinical presentations of seven patients with mutations in CYP11A1 encoding the cholesterol side-chain cleavage enzyme, P450scc", J Clin Endocrinol Metab, 98, pp.713~720 (2013)
  18. Parajes S, "A novel entity of clinically isolated adrenal insufficiency caused by a partially inactivating mutation of the gene encoding for P450 side chain cleavage enzyme (CYP11A1)", J Clin Endocrinol Metab, 96, pp.E1798~E1806 (2011)
  19. Baker BY, "Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia", J Clin Endocrinol Metab, 91, pp.4781~4785 (2006)
  20. Metherell LA, "Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency", J Clin Endocrinol Metab, 94, pp.3865~3871 (2009)
  21. Sahakitrungruang T, "Clinical, genetic, and functional characterization of four patients carrying partial loss-of-function mutations in the steroidogenic acute regulatory protein (StAR)", J Clin Endocrinol Metab, 95, pp.3352~3359 (2010)
  22. Fujieda K, "Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita", J Steroid Biochem Mol Biol, 85, pp.483~489 (2003)
  23. Nakae J, "Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia", Hum Mol Genet, 6, pp.571~576 (1997)
  24. 김찬종, "Congenital lipoid adrenal hyperplasia", Annals of Pediatirc Endocrinology & Metabolism, 19(4), pp.179~183 (2014), 대한소아내분비학회
  25. Chen X, "A genetic isolate of congenital lipoid adrenal hyperplasia with atypical clinical findings", J Clin Endocrinol Metab, 90, pp.835~840 (2005)
  26. Fluck CE, "A novel mutation L260P of the steroidogenic acute regulatory protein gene in three unrelated patients of Swiss ancestry with congenital lipoid adrenal hyperplasia", J Clin Endocrinol Metab, 90, pp.5304~5308 (2005)
  27. Lorence MC, "Human 3beta-hydroxysteroid dehydrogenase", delta 5→4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation, Endocrinology, pp.1990, 126[DOI]
  28. Lorence MC, "Structural analysis of the gene encoding human 3beta-hydroxysteroid dehydrogenase", delta 5→4-isomerase, 1990, pp.4, 1850~1855
  29. Lachance Y, "Characterization of human 3 betahydroxysteroid dehydrogenase", delta 5-delta 4-isomerase gene and its expression in mammalian cells, 1990, pp.265, 20469~20475
  30. Bongiovanni AM., "The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase", J Clin Invest, 41, pp.2086~2092 (1962)
  31. Simard J, "Molecular biology of the 3beta-hydroxysteroid dehydrogenase", delta5-delta4 isomerase gene family, 2005, pp.26, 525~582
  32. Jeandron DD, "A novel homozygous Q334X mutation in the HSD3B2 gene causing classic 3β-hydroxysteroid dehydrogenase deficiency: an unexpected diagnosis after a positive newborn screen for 21-hydroxylase deficiency", Horm Res Paediatr, 77, pp.334~338 (2012)
  33. Moisan AM, "New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency:identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes", J Clin Endocrinol Metab, 84, pp.4410~4425 (1999)
  34. Chang YT, "Hypothalamic-pituitary-gonadal axis function in pubertal male and female siblings with glucocorticoidt re ated nons a lt -wa st ing 3 be t a -hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia", J Clin Endocrinol Metab, 77, pp.1251~1257 (1993)
  35. Sanchez R, "Detection and functional characterization of the novel missense mutation Y254D in type II 3 betahydroxysteroid dehydrogenase (3 beta HSD) gene of a female patient with nonsalt-losing 3 beta HSD deficiency", J Clin Endocrinol Metab, 78, pp.561~567 (1994)
  36. Mermejo LM, "Refining hormonal diagnosis of type II 3beta-hydroxysteroid dehydrogenase deficiency in patients with premature pubarche and hirsutism based on HSD3B2genotyping", J Clin Endocrinol Metab, 90, pp.1287~1293 (2005)
  37. Peter M, "A case of 11beta-hydroxylase deficiency detected in a newborn screening program by second-tier LC-MS", MS, 2008, pp.69, 253~256
  38. White PC, "A mutation in CYP11B1 (Arg-448----His)associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin", J Clin Invest, 87, pp.1664~1667 (1991)
  39. Nimkarn S, "Steroid 11beta-hydroxylase deficiency congenital adrenal hyperplasia", Trends Endocrinol Metab, 19, pp.96~99 (2008)
  40. Zhu YS, "Mutations in CYP11B1 gene: phenotype-genotype correlations", Am J Med Genet A, 122A, pp.193~200 (2003)
  41. Joehrer K, "CYP11B1 mutations causing nonclassic adrenal hyperplasia due to 11 beta-hydroxylase deficiency", Hum Mol Genet, 6, pp.1829~1834 (1997)
  42. Reisch N, "A diagnosis not to be missed: nonclassic steroid 11β-hydroxylase deficiency presenting with premature adrenarche and hirsutism", J Clin Endocrinol Metab, 98, pp.E1620~E1625 (2013)
  43. Hampf M, "Unequal crossing-over between aldosterone synthase and 11betahydroxylase genes causes congenital adrenal hyperplasia", J Clin Endocrinol Metab, 86, pp.4445~4452 (2001)
  44. Chung BC, "Cytochrome P450c17 (steroid 17alpha-hydroxylase", 17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues, 1987, pp.84, 407~411
  45. Picado-Leonard J, "Cloning and sequence of the human gene for P450c17 (steroid 17 alphahydroxylase", 17,20 lyase): similarity with the gene for P450c21, 1987, pp.6, 439~448
  46. Sahakitrungruang T, "Novel P450c17 mutation H373D causing combined 17alphahydroxylase", 17,20-lyase deficiency, 2009, pp.94, 3089~3092
  47. Geller DH, "The genetic and functional basis of isolated 17,20-lyase deficiency", Nat Genet, 17, pp.201~205 (1997)
  48. Sherbet DP, "CYP17 mutation E305G causes isolated 17,20-lyase deficiency by selectively altering substrate binding", J Biol Chem, 278, pp.48563~48569 (2003)
  49. Fluck CE, "Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome", Nat Genet, 36, pp.228~230 (2004)
  50. Scott RR, "Genetic and clinical features of p450oxidoreductase deficiency", Horm Res, 69, pp.266~275 (2008)
  51. Sahakitrungruang T, "Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients", J Clin Endocrinol Metab, 94, pp.4992~5000 (2009)
  52. Hershkovitz E, "Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency", J Clin Endocrinol Metab, 93, pp.3584~3588 (2008)
  53. Arlt W, "Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis:analytical study", Lancet, 363, pp.2128~2135 (2004)
  54. Huang N, "Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis", Am J Hum Genet, 76, pp.729~749 (2005)
  55. Fukami M, "Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35Japanese patients", J Clin Endocrinol Metab, 94, pp.1723~1731 (2009)
  56. Krone N, "Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency", J Clin Endocrinol Metab, 97, pp.E257~E267 (2012)

관련 논문AI추천

Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiencyGu Hwan Kim, Han-Wook Yoo, Jin-Ho Choi대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2016 · 제21권 제1호Two cases of 17α-hydroxylase/17,20-lyase deficiency caused by the CYP17A1 mutationChae Hyun Wook, Choi Han Saem, Kim Ho-Seong, Kwon Ahreum, Lee Hae In, Song Kyung Chul, Suh Junghwan대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2021 · 제26권 제1호Compound heterozygosity for a whole gene deletion and p.R124C mutation in CYP21A2 causing nonclassic congenital adrenal hyperplasiaHamza Nasir, Naeem Haque, Salman Kirmani, Stefan K. Grebe, Syed Ibaad Ali대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2018 · 제23권 제3호Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency최진호, Cheon Chong-Kun, Kim Gu-Hwan, Ko Cheol Woo, Lee Yena, Moon Jung Eun, Oh Arum, Park Sook-Hyun, Yoo Han-Wook대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2020 · 제25권 제2호Molecular basis and genetic testing strategies for diagnosing 21-hydroxylase deficiency, including CAH-X syndromeChoi Jin-Ho, Kim Gu-Hwan, Kim Ja Hye, Yoo Han-Wook대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2023 · 제28권 제2호Prevalence of CYP17A1 gene mutations in 17α-hydroxylase deficiency in the Chinese Han populationCaini Fan, Fansen Meng, Fujia Liu, Haiying Zhao, Hao Wang, Ling Li, Menglin Wang, Min Liu대한고혈압학회 · Clinical Hypertension2019 · 제25권 제4호

이 간행물의 다른 논문 (9건)