JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
Newborn Screening for Congenital Adrenal Hyperplasia: Review of Undetected Cases in Louisiana
Dania Felipe, MD, Joseph Ortenberg, MD, Ricardo Gomez, MD, Aaron Martin, MD, MPH, Robin Ortenberg, MD, Michael Marble, MD
INTRODUCTION
vaginal opening. Newborn screen done at one day 23 hours old was 17-OHP -36 ng/ml (normal <50 ng/ml FIA, DELFIA, Perkin Elmer Life and Analytical Sciences, Turku, Finland). She was referred to Genetics clinic at 10 months of age for the same concern. On exam, length 76.5 cm (95 th percentile), weight 9.1 kg (50 th percentile), clitoris was enlarged measuring ~2cm, clitoriswidthwas 1cm, she had a small vaginal opening, posterior fusion of labia. Laboratory evaluation included 17-OHP-1650 ng/dl (normal<91) by high performance liquid chromatography (Esoterix, Calabasas Hills, CA). Repeat 17-OHP was 774 ng/dl, total testosterone 6.3 ng/dl (<2.5- 10), dehydroepiandrosterone sulfate (DHEA-S) 20 ug/dl (<49), plasma renin activity (PRA) 1559 ng/dl/h (235-3700). Bone age was one year six months at chronologic age 10 months. Pelvic ultrasound revealed a normal prepubertal uterus and ovaries. Karyotype result was 46,XX. She subsequently underwent feminizing genitoplasty. Patient 2 is the sister of patient 1 born at 40 weeks of age with no complications. Birth weight was 3.75 kg. She was noted at birth to have ambiguous genitalia. On day two of life, sodium was 140 mmol/L, potassium 5.1 mmol/L, DHEA >1500 mcg/dl. Pelvic ultrasound revealed a normal uterus. Her newborn screen was also normal. She had clitoroplasty at 6 months of age. Patient 3 is a four week old female born at term to a mother with PCOS (?undiagnosed CAH) who was noted by pediatrician to have labial fusion and an enlarged clitoris measuring 1 X 0.7 cm. Her newborn screen done at 27 hours of age was normal but her confirmatory 17-OHP was elevated 5700 ng/dl. Despite her late presentation, she behaved as a salt-waster as evidenced by elevated renin level and is a carrier for F306+1nt, Q318X, mutations known to cause classic CAH (Table 1). Patient 4 was noted to have pubic hair at age three years six months. Laboratory evaluation revealed an elevated 17-OHP and a V281L mutation on genetic testing.
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by an enzyme defect which causes disruption in corticosteroid and mineralocorticoid synthesis. Most CAH cases are caused by 21-hydroxylase deficiency encoded by a mutation in the CYP21A2 gene. The worldwide incidence of CAH is 1:15,000 (6.6 per 100,000) to 1:18,000, highest frequency found in Ashkenazi Jews, Alaskan natives and people from Brazil. 1 The early recognition of CAH by newborn screen avoids the life-threatening adrenal crisis in males and decreases the number of virilized female infants falsely identified as males. 2 Implementation of the neonatal screening program is due to the efforts of Robert Guthrie in the 1960s. 3 Screening for CAH was first introduced in the state of Louisiana in 2006 and since then, we have had 1053 presumptive positives and 35 confirmed cases for an incidence of 1.5-14. 5 in 100,000 persons per year. Well recognized causes of a false positive screen include early collection time of the sample, preterm or severely ill babies, stress, poor kidney function, or physiologically delayed expression of the 11ß-hydroxylase that causes transiently increased concentrations of 17-OHP. 4 This brief report describes several patients from our Endocrinology Clinics at Children’s Hospital with virilizing CAH missed by the Louisiana newborn screening program.
CASE PRESENTATION
Patient 1 was referred to our Endocrinology Clinic at three weeks of age due to ambiguous genitalia. She is an African-American femaleborn at 39weeks to aG3P3mother withno complications. Birth weight was 4 kg. Parents are nonconsanguineous. At the time of this visit to our pediatric endocrine clinic, shewas feeding well and had gained weight appropriately. On exam, length was 54.7 cm (90 th percentile), weight 4.3 kg (75 th percentile), no clitoromegaly was noted but she did have a small but patent
J La State Med Soc VOL 170 JANUARY/FEBRUARY 2018 15
Made with FlippingBook Digital Publishing Software