JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
Pt
17OHP Screening level (ng/dl)
17OHP at Dx (ng/dl)
Age at Dx Sex Presentation Na
K mmol/L
Renin Ng/dl/h
Genetic Testing
mmol/L
3600 (nl<5000)
1650
10m F
Clitoromegaly 138
4.6
1559
I172N, A479L, frameshift mutation at codon 171
1
3200 (nl<4000)
1320
2 days old F
Clitoromegaly, posterior labial fusion
138
6.4
n/a
n/a
2
4400 (nl<4000)
5700
1 month F
Clitoromegaly 136
5.1
5111
I172N, V281L, F306+1nt, Q318X
3
1700 (nl<8000)
135 at0 min 926 at60 min
3.5 y
F
Premature adrenarche
142
n/a
n/a
V281L
4
1500 (nl<8000)
20 at0 min 397 at60 min
4 y
F
Premature adrenarche
P453s
5
Table 1: Summary of patients unrecognized by Louisiana newborn screen
Patient 5 was noted to have pubic hair at age 4. She has a sister who had a similar presentation and her mother required fertility treatment with clomiphene. On ACTH stimulation test using Cosyntropin 250 mcg IV, baseline 17-OHP was 20 ng/ dl, DHEAS 95 mcg/dl, testosterone 8.5 ng/dl, adrostenedione 31 ng/dl, and at 60 minutes laboratory results were 17-OHP 396 ng/dl, and androstenedione 64 ng/dl. Both the method of the determination of 17-OHP and cutoff levels were altered at different points during the screening period.
Wisconsin identified 8 patients diagnosed with CAH to have a normal newborn screen. 5 The age at diagnosis ranged from birth to 54 months, with 5 infants identified by three months of age, and the other three identified after 12 months. Five of the seven female patients were referred for evaluation of genital abnormality, the one male patient was evaluated for premature adrenarche at age four, one infant had an elevated 17-OHP on repeat newborn screen at one week of life and the last patient had a repeat newborn screen for an abnormal trypsinogen level that revealed an elevated 17-OHP. A similar study in Sweden revealed seven infants with false negative results who all carried the simple virilizing form of the disease. 6 A study in Texas compared screened newborns versus unscreened infants in the neighboring states of Oklahoma and Arkansas. 7 The incidence of diagnosis of salt wasting CAH per 100,000 newborns was similar in both cohorts. The unscreened group had fewer male newborns diagnosed with salt-wasting CAH and the median age at diagnosis was later in the unscreened group - 26 days versus 12 days in the screened group. A possible explanation for the lower number of affected males versus females is that males often present in a salt wasting crisis and may die before a diagnosis is established.
DISCUSSION
This report summarizes pediatric cases with CAH not identified by the Louisiana newborn screen from 2006-2016. When a presumptive positive is identified, the primary care provider is notified either by a phone call and/or written communication. A second screen is collected but depending on the clinical scenario, an evaluation might be necessary prior to this collection. If a repeat screen is positive, a visit to a pediatric endocrinologist is required for confirmation. Most newborn screen programs use enzyme-linked immunosorbent assays (ELISA) to determine levels of 17-OHP. This test has a low specificity and a low positive predictive value (PPV). After implementation of the program in 1993, a study in
16 J La State Med Soc VOL 170 JANUARY/FEBRUARY 2018
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