1416 Scholars Journal of Applied Medical Sciences (SJAMS) ISSN 2320-6691 (Online) Sch. J. App. Med. Sci., 2015; 3(3F):1416-1421 ISSN 2347-954X (Print) ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) www.saspublisher.com Research Article Congenital Adrenal Hyperplasia due to 21--Hydroxylase Deficiency in Saudi Arabia Nasir A. M. Al Jurayyan 1 , Hessah M.N. Al Otaibi 2 , Amer O. Al Ali 3 , Osamah A. Al Ayed 4 , Amal A. Al Hakami 5 , Sharifa D. A. Al Issa 6 , Haya M. Bin Nafisah 7 1 Professor of Pediatric and Consultant Pediatric Endocrinologist, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia 2 Consultant Pediatric Endocrinologist, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia 3 Senior Fellow in Pediatric Endocrinology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia 4, 5 Fellow in Pediatric Endocrinology College of Medicine and King Khalid University Hospital King Saud University, Riyadh, Saudi Arabia 6 Senior Registrar in Pediatric Endocrinology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia 7 Resident in Pediatric Endocrinology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia *Corresponding author Dr. Nasir A.M. Al Jurayyan Abstract: Congenital adrenal hyperplasia (CAH) due to 21--hydroxylase deficiency is a common endocrine disorder accounting for more than 90 percent of CAH cases. As a result to the hormonal imbalance salt-wasting may occur, and predisposes affected females to prenatal development of genital ambiguity. This article discusses the clinical presentation, diagnosis and management of this disorder and highlights new developments, including genotype- phenotype correlations, screening, gene-specific pre-natal diagnosis and pre-natal therapy. Keywords: Congenital adrenal hyperplasia, Saudi Arabia, 21--hydroxylase, Deficiency. INTRODUCTION Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex (Fig. 1). The enzymes involved are 21--hydroxylase, 11-- hydroxylase, 17-hydroxylase, 3-hydroxysteroid dehydrogenase, and 20,22desmolase. The most common enzyme defect is 21-hydroxylase that accounts for almost 90% of cases. The fundamental defect in CAH is the inability to synthesize cortisol adequately. Inefficient cortisol synthesis signals the hypothalamus and pituitary to increase corticotrophin releasing hormone (CRH) and adrenocorticotrophin hormone (ACTH). As a result, the adrenals become hyperplastic and produce an excess amount of sex hormone precursors, which do not require 21-hydroxylase for their synthesis. These precursors, progesterone and 17 hydroxyprogesterone, are further metabolized to active androgens, testosterone, and dihydrotestosterone, and to a lesser extent oestrogens-oesterone and oestradiol. The effect is prenatal virilization of girls and rapid somatic growth with early epiphyseal fusion in both genders the so called “simple virilization”. This can be associated with a life-threatening hyponatremic dehydration and hyperkalaemia and are called “salt-wasters” (Fig. 2) [1- 13]. A mild non-classical forms (late onset) occurs with partial enzyme deficiency. The females usually present late in life with signs of androgen excess and without neonatal genital ambiguity. Clinical features in childhood may include precocious puberty and may present as an adultand may be presented with hirsutism, menstrual irregularity, infertility and acne. Some patients remain asymptomatic. They may present as well with precocious sexual development. The 21- hydroxylase gene CYP21 is located on the short arm of chromogene 6. A pseudo-gene CYP21 p is located downstream close to CYP21. Diseases resulting from mutations are due to CYP21 p acquiring portions of CYP 21. Many mutations causing disease have been reported [14, 15].