Multiple Positive Sweat Chloride Tests in an Infant Asymptomatic for Cystic Fibrosis

Steven W. Cotten, PhD; Laura M. Bender, PhD; Monte S. Willis, MD, PhD

Lab Med. 2012;43(2):1-5.

Abstract and Introduction

Abstract

Clinical History
Patient: 1-month-old male.
Chief Complaint: Multiple positive sweat chloride tests in the absence of signs or symptoms suggestive of cystic fibrosis (CF).
History of Present Illness: The patient was referred for sweat chloride testing after a positive newborn screen for immunoreactive trypsinogen (IRT). Immunoreactive trypsinogen is suggestive of CF when the value is within the top 5% of a period-specific floating cutoff value^[1] (Figure 1). The patient's sweat chloride levels were elevated (>60 mmol/L). Preliminary screening for CF transmembrane conductance regulator (CFTR) mutations using a 40 mutation screen identified 1 mutation in intron 11 (1585 -1G>A, legacy name 1717 -1G>A). Subsequent full gene CFTR sequencing revealed a second CFTR mutation in intron 22.
Past Medical History: The infant was full term, weighing 8 lbs 6 oz at birth, and experienced an uncomplicated delivery. The infant was discharged following a standard 2-day stay in the newborn nursery.
Physical Exam: A temperature of 36.4°C (axillary), blood pressure of 120/80 mm Hg, heart rate of 148, and respirations of 40 per minute were measured for the patient. The patient's O₂ saturation was 100% on room air. The patient's length was 61.2 cm (90th percentile), weight 6.27 kg (95th percentile), and head circumference was 39.7 cm (50th percentile). His weight-to-length ratio was at the 50th percentile. The patient appeared healthy with no labored respiration and no apparent digestive issues.
Drug History: None
Family History: No family history of chronic diseases.
Principal Laboratory Findings: The patient underwent sweat chloride testing on sweat collected by pilocarpine iontophoresis from both arms (Table 1). These tests were repeated several weeks later yielding similar results (not shown).

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Table 1. Initial Laboratory Testing for CF Performed on the Patient
Test	Patient Result	Reference Range (≤6 Months)
Sweat quanity (right arm)	649 mg	Minimum of 75 mg required
Sweat quantity (left arm)	616 mg
Sweat chloride (right)	77 mmol/L	≤29, CF unlikely
		30–59, CF possible
		≥60, CF likely
Sweat chloride (left)	74 mmol/L
40 allele CFTR DNA panel	1585–1G>A	N/A

Table 2. Additional CF Testing Performed on the Patient
Test	Patient Result	Reference Range
CFTR Full Gene Sequencing	1585 -1G>A	N/A
	3717 +40A>G	N/A
Serum sodium	136	135–145 mmol/L
Serum chloride	103	98–107 mmol/L
TSH	3.87	0.50–6.50 microIU/mL
Total T4	9.5	7.2–15.0 mcg/dL
Aldosterone	17	17–154 ng/dL
Vitamin A (serum)	17.9	11.3–64.7 mcg/dL
Vitamin D (serum)	14	<10 ng/mL, severe deficiency
		10–24 ng/mL, moderate to mild deficiency
		25–80 ng/mL, optimum level
		>80 ng/mL, elevated level (possible toxicity)
Vitamin E (serum)	12.4	3.8–18.4 mg/L

Table 3. Possible Indications for *CFTR* Allele Analysis in 3 Clinical Scenarios
Diagnostic Testing	Carrier Screening	Prenatal Screening
Newborn screening programs	Partners of individuals with positive family history	Preimplantation testing
Possible diagnosis of CF	Partners of CBAVD males	Positive family history or for couples having a CF mutation in both partners
Definite diagnosis of CF	General population of reproductive couples	Echogenic bowel in fetus during second trimester
Congenital bilateral absence of the vas deferens (CBAVD) in males	Premarital population, to assist in selection of a mate Positive family history Gamete donors

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