Background: Newborn screening for congenital adrenal hyperplasia (CAH) is based on the determination of 17-hydroxyprogesterone (17OHP) on blood and its need is confirmed by the most recent guidelines on the subject. In Italy this screening is not mandatory, and its application is on a regional basis. Among its disadvantages, it is well known the high frequency of false-positives, in particular in premature babies and those born small for gestational age. However, there are a number of subjects who are false-negatives (FN), with the risk of late diagnosis and development of complications.
Case report: A 4-year-old boy presented with pubic hair, body odor and acne noted one year earlier. At clinical examination, height was 125.1 cm (+3.85 SDS, target height +0,70 SDS), weight 25,1 kg (+2 SDS) and he had mild acne in his face. He was Tanner stage 2 (G2PH3, testicular volume 4 ml bilaterally). Bone age was 12-13 years. In his previous medical history, he was recalled for CAH screening performed at 3 days of life (17OHP 35 nmol/l, n.v.<18), showing normal values of 17OHP at 6 days of life (8 nmol/l).He was a first-born from unrelated parents without significant illnesses. Pregnancy and vital parameters at birth were regular; birth weight was 3660 g. Due to the clinical picture and blood tests (basal 17OHP 158 ng/ml, renin 303.6 mUI/l -n.v. 2.8-39-, aldosterone 453 ng/l -n.v. 12-240-, normal sodium and potassium levels, LH peak after GnRH test 5,3 UI/l, FSH peak 1.9 UI/l), a diagnosis of classical CAH complicated by a central precocious puberty was made. Replacement therapy with hydrocortisone and fludrocortisone and puberty blocking therapy were started, with good clinical response. Treatment with human GH was also started to improve height prognosis. From the molecular investigation of the CYP21A2 gene, the patient resulted hemizygous for the p.l173N variant.
Discussion: Newborn screening has still limitations in the diagnosis of CAH. FN are produced for reasons still unclear including issues in timing and/or sensibility of laboratory tests. FN are underestimated, also due to the lack of an effective reporting system for patients with late diagnoses; furthermore, they are underreported in literature (Votava et al,2005; Schreiner et al,2008; Sarafoglou et al,2012). Therefore, pediatricians should be aware that a negative newborn screening does not rule out the manifestation of classical CAH during later stages of life.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology