Ann Pediatr Endocrinol Metab.  2013 Jun;18(2):90-94. 10.6065/apem.2013.18.2.90.

Central precocious puberty in a patient with X-linked adrenal hypoplasia congenita and Xp21 contiguous gene deletion syndrome

• Koh JW
• Kang SY
• Kim GH
• Yoo HW
• Yu J

• KMID: 2047468
• DOI: http://doi.org/10.6065/apem.2013.18.2.90

Abstract

X-linked adrenal hypoplasia congenita is caused by the mutation of DAX-1 gene (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1), and can occur as part of a contiguous gene deletion syndrome in association with glycerol kinase (GK) deficiency, Duchenne muscular dystrophy and X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) gene deficiency. It is usually associated with hypogonadotropic hypogonadism, although in rare cases, it has been reported to occur in normal puberty or even central precocious puberty. This study addresses a case in which central precocious puberty developed in a boy with X-linked adrenal hypoplasia congenita who had complete deletion of the genes DAX-1, GK and IL1RAPL1 (Xp21 contiguous gene deletion syndrome). Initially he was admitted for the management of adrenal crisis at the age of 2 months, and managed with hydrocortisone and florinef. At 45 months of age, his each testicular volumes of 4 mL and a penile length of 5 cm were noted, with pubic hair of Tanner stage 2. His bone age was advanced and a gonadotropin-releasing hormone (GnRH) stimulation test showed a luteinizing hormone peak of 8.26 IU/L, confirming central precocious puberty. He was then treated with a GnRH agonist, as well as steroid replacement therapy. In Korea, this is the first case of central precocious puberty developed in a male patient with X-linked adrenal hypoplasia congenita.

Keyword

X-linked adrenal hypoplasia congenita; Nuclear Receptor DAX-1; Precocious puberty; Central

MeSH Terms

Adrenal Hyperplasia, Congenital
Adrenal Insufficiency
DAX-1 Orphan Nuclear Receptor
Fludrocortisone
Gene Deletion
Genetic Diseases, X-Linked
Glycerol Kinase
Gonadotropin-Releasing Hormone
Hair
Humans
Hydrocortisone
Hypogonadism
Interleukin-1
Korea
Luteinizing Hormone
Male
Muscular Dystrophy, Duchenne
Puberty
Puberty, Precocious
Adrenal Hyperplasia, Congenital
Adrenal Insufficiency
DAX-1 Orphan Nuclear Receptor
Fludrocortisone
Genetic Diseases, X-Linked
Glycerol Kinase
Gonadotropin-Releasing Hormone
Hydrocortisone
Interleukin-1
Luteinizing Hormone

Figure

• 

  Fig. 1 Changes of height and weight z scores according to chronologic and bone ages. Initially, weight and height z scores based on bone age were lower than average, but both of them are now in around average levels. Arrows represent the period of gonadotropin-releasing hormone therapy which are from 46 months to 57 months, from 64months to 103 months, and from 110 months till now.

Reference

1. Zanaria E, Muscatelli F, Bardoni B, Strom TM, Guioli S, Guo W, et al. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature. 1994; 372:635–641. PMID: 7990953.

2. Walker AP, Chelly J, Love DR, Brush YI, Recan D, Chaussain JL, et al. A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes. Hum Mol Genet. 1992; 1:579–585. PMID: 1301166.

3. Muscatelli F, Strom TM, Walker AP, Zanaria E, Recan D, Meindl A, et al. Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature. 1994; 372:672–676. PMID: 7990958.

4. Loke KY, Poh LK, Lee WW, Lai PS. A case of X-linked adrenal hypoplasia congenita, central precocious puberty and absence of the DAX-1 gene: implications for pubertal regulation. Horm Res. 2009; 71:298–304. PMID: 19339795.

5. Darcan S, Goksen D, Ozen S, Ozkinay F, Durmaz B, Lalli E. Gonadotropin-dependent precocious puberty in a patient with X-linked adrenal hypoplasia congenita caused by a novel DAX-1 mutation. Horm Res Paediatr. 2011; 75:153–156. PMID: 20975255.

6. Sikl H. Addison's disease due to congenital hypoplasia of the adrenals in an infant aged 33 days. J Pathol Bacteriol. 1948; 60:323. PMID: 18099667.

7. Reutens AT, Achermann JC, Ito M, Ito M, Gu WX, Habiby RL, et al. Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita. J Clin Endocrinol Metab. 1999; 84:504–511. PMID: 10022408.

8. Hay ID, Smail PJ, Forsyth CC. Familial cytomegalic adrenocortical hypoplasia: an X-linked syndrome of pubertal failure. Arch Dis Child. 1981; 56:715–721. PMID: 7197507.

9. Habiby RL, Boepple P, Nachtigall L, Sluss PM, Crowley WF Jr, Jameson JL. Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalmic and pituitary defects in gonadotropin production. J Clin Invest. 1996; 98:1055–1062. PMID: 8770879.

10. Seminara SB, Achermann JC, Genel M, Jameson JL, Crowley WF Jr. X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females. J Clin Endocrinol Metab. 1999; 84:4501–4509. PMID: 10599709.

11. Calvari V, Alpigiani MG, Poggi E, Podesta B, Camerino G, Lorini R. X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism: report on new mutation of the DAX-1 gene in two siblings. J Endocrinol Invest. 2006; 29:41–47. PMID: 16553032.

12. Domenice S, Latronico AC, Brito VN, Arnhold IJ, Kok F, Mendonca BB. Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene. J Clin Endocrinol Metab. 2001; 86:4068–4071. PMID: 11549627.

13. Partsch CJ, Sippell WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update. 2001; 7:292–302. PMID: 11392376.

14. Wittenberg DF. Familial X-linked adrenocortical hypoplasia association with androgenic precocity. Arch Dis Child. 1981; 56:633–636. PMID: 7023391.

15. Katsumata N, Tanae A, Shinagawa T, Nimura A, Horikawa R, Tanaka T. Precocious puberty in patient with congenital adrenal hypoplasia congenital (abstract P02-512). In : Proceedings of the 79th Annual Meeting of the Endocrine Society; 1997 June 11-14; Minneapolis, MN, USA. Chevy Chase, MD: The Endocrine Society;1997.

16. Durmaz E, Turkkahraman D, Berdeli A, Atan M, Karaguzel G, Akcurin S, et al. A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree. J Pediatr Endocrinol Metab. 2013; 26:551–555. PMID: 23585174.