Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 6-3

Twenty-Day-Old Girl



This 20-day-old Caucasian female infant was referred to the emergency department by her primary care doctor for failure to thrive. She was at full-term gestation, 2.53 kg, born via spontaneous vaginal delivery with no complications during pregnancy. In the first 36 hours of life, she had poor feeding because of poor suck. She had normal bowel movements and normal urine output in the nursery. After 36 hours of life, she began to feed well, and was discharged with her mother. During the last 3 weeks, the baby had been seen several times by her primary physician for weight checks. She failed to regain her birth weight. She was feeding 2.5 to 3 ounces every 2-3 hours (approximately eight 3 ounce bottles per day). Formula was being made from powder and mixed appropriately. There was no emesis, arching, or irritability with feeds. She has had loose seedy stools for 2 days prior to admission. No blood was noted in the stool. There was nasal congestion but no fever. There were no ill contacts except that the mother had an illness with fever and headache one week prior to this visit.


The prenatal history was remarkable for maternal tobacco use (one-half pack per day) but no illicit drug use. Peripartum testing for group B Streptococcus, hepatitis B, and HIV were negative. The prenatal ultra-sound revealed normal fetal movements. The mother took prenatal vitamins but no other medications during pregnancy. The infant was born by vaginal delivery complicated only by the presence of meconium at delivery. The Apgar scores were not known.

There was no family history of still births or miscarriages. There were no known metabolic disorders, congenital heart disease, seizure disorders, or neurologic disease. There was no history of cystic fibrosis.


T 36.9°C; HR 160 bpm; RR 40/min; BP 96/62 mmHg

Weight 2.42 kg (<5 percentile); Length 46 cm (<5 percentile); Head circumference 35 cm (10 percentile)

In general, the patient was cachetic but active. The anterior fontanel was open and flat. The posterior fontanel was approximately 1 cm wide. There were no dysmorphic facial features. The pupils were reactive bilaterally. The oropharynx was clear; specifically, there was no thrush. There was no lymphadenopathy. The heart and lung sounds were normal. The abdomen was soft. The liver edge was palpable 1 cm below the right costal margin. The skin was mottled and pale. A 1-cm hemangioma was located on the left parietal area. The neurologic examination was normal.


Serum sodium, 136 mEq/L; potassium, 5.5 mEq/L; chloride, 100 mEq/L; bicarbonate, 28 mEq/L; blood urea nitrogen, creatinine, glucose, calcium, magnesium, and phosphorus were normal.


The 20-day-old infant with moderate malnutrition and failure to thrive was admitted for inpatient evaluation, including strict calorie counts and feeding observation. During the next 2 days, she had adequate caloric intake (as much as 180-200 kcal per kg per day) without documented weight gain. She was also noted to have increased stool output, with more output than intake. Her stools were positive for reducing substances. The stool pH was 5.5. All stools were heme negative.



The differential diagnosis in this case was broad. When feeding the baby, a poor suck and swallow was noted. This difficulty with intake was questioned as to whether it was a primary problem (e.g., neuropathy, spinal-muscle atrophy) or secondary due to poor nutrition and weakness. When the child was fed, she gained more strength but still failed to gain weight. When no weight gain was noted despite adequate caloric intake, malabsorption was considered.


Sweat tests were obtained, which showed good sweat volumes over the collection time of 30 minutes. The sweat chloride was 95 and 105 at the two sites sampled (normal <40, borderline 40-60, abnormal >60). The sweat test was repeated and was again abnormal. The patient was diagnosed with cystic fibrosis (CF). Baseline chest X-ray was normal. She was started on supplemental enzymes, as well as vitamin supplementation and nebulized albuterol and cromolyn. She did well with supplemental enzymes, documenting excellent catchup growth while in the hospital. The diagnosis of cystic fibrosis was considered when a normal, and eventually a supernormal, calorie intake was achieved and the infant failed to gain weight. This clinical trial resulted in the suspicion of a malabsorption problem and cystic fibrosis was considered as the most common cause of malabsorption.


The incidence of cystic fibrosis varies by population tested. Overall, it is the most common life-shortening inherited disease in North America. Cystic fibrosis is inherited as an autosomal recessive disease. Several gene sites have been recognized. The most important is the σF508 on the long arm of chromosome 7. In those of Northern European extraction, it occurs in 1 in every 2500 live births. Approximately 4% of whites are carriers of a cystic fibrosis gene. The manifestations of cystic fibrosis are very varied. Table 6-6 shows diagnostic criteria for cystic fibrosis.

TABLE 6-6. Diagnostic criteria for cystic fibrosis.a


• One or more characteristic phenotypic features (chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, sweat salt loss syndrome, male infertility)

• CF in a sibling or a positive newborn screen

Laboratory Evidence of Abnormal CFTR/CFTR Function

• A positive sweat test (a sweat chloride concentration >60 meq/L on a sample of at least 100 mg, obtained after maximal stimulation by pilocarpine iontophoresis

• Identification of two CFTR mutations known to cause CF

• Diagnostic nasal potential difference

a Diagnosis requires at least one from each column.


The clinical presentation and age of presentation are varied. Manifestations may be evident at birth but in some cases have not become apparent until fertility evaluations in young adulthood have led to the diagnosis. All of the following systems may be involved: gastrointestinal, sweat glands, respiratory tract, reproductive, orthopedic, and endocrine/metabolic (hyperglycemia). Failure to thrive is one of the most frequent presenting signs. Table 6-7 shows the indications for sweat testing and also lists clinical findings in patients with cystic fibrosis.

TABLE 6-7. Indications for sweat testing.

Gastrointestinal Tract

Chronic diarrhea


Meconium ileus

Meconium plug syndrome

Rectal prolapse

Cirrhosis/portal hypertension

Prolonged neonatal jaundice


Deficiency of fat-soluble vitamins (especially A, E, K)

Respiratory Tract


Nasal polyps

Pansinusitis on radiographs


Chronic cough

Recurrent bronchiolitis

Recurrent wheezing

Intractable “asthma”

Recurrent or persistent atelectasis

Obstructive pulmonary disease

Staphylococcal pneumonia

Pseudomonas aeruginosa (especially mucoid colony types) recovered from throat, sputum, or bronchoscopic cultures


Digital clubbing

Family history of cystic fibrosis

Failure to thrive

Hyponatremic, hypochloremic alkalosis

Severe dehydration incompatible with

clinical history

Heat prostration

“Tastes salty”

Male infertility

Source: Adapted from: Orenstein DM. Cystic fibrosis. In: Rudolph CD, Rudolph AM, eds. Rudolph’s Pediatrics. 21st ed. New York: McGraw-Hill; 2003.


Diagnostic approach is based on phenotypic presentation plus laboratory confirmation. The laboratory confirmation is usually based on a positive sweat test with a sweat concentration greater than 60 meq/L on a sweat sample of at least 100 mg. Genetic testing is also available (Table 6-6).

Tissue typing gives the indication for sweat testing which also shows the varied manifestations. Care must be taken because there may be causes of false positive and false negative testing. Indications for sweat testing are presented in Table 6-7.

Newborn screening. Earlier diagnosis of cystic fibrosis is possible in some cases since newborn infants with cystic fibrosis have elevated blood immunoreactive trypsinogen levels caused by obstructed pancreatic ductules. Infants with immunoreactive trypsinogen levels above the 99th percentile typically undergo confirmatory sweat testing and, in some cases, screening for the principal CF gene mutation (ΔF508).


Treatment is best accomplished with a multidisciplinary team and involves treatment of the lungs, GI nutrition, and psychosocial aspects of the disease with the institution of care being delivered at specialized multidisciplinary center. While much research has been directed toward aggressively treating lung disease early in life to improve long-term pulmonary function and survival, recently the nutritional aspects of young children with cystic fibrosis have been stressed as important to outcomes. Konstan et al. demonstrated that nutritional status in children with cystic fibrosis at 3 years of age correlates with pulmonary symptoms later in life. In an observational study of 931 children with cystic fibrosis, they found that children with weight-for-age below the 5th percentile at age 3 years had lower pulmonary function at age 6 compared with those above the 75th percentile. Thus, poor growth and nutritional status, in addition to lung disease early in life, contribute to pulmonary function later in life.

The median survival rate has steadily increased from 14 years in 1969 to 32 years in 2000. Gene replacement therapy is under active investigation. Prenatal screening is being attempted and appears to have a high degree of patient satisfaction and understanding. Follow-up in a special cystic fibrosis center is important in order that multidisciplinary services be aimed at nutrition, pulmonary status, and avoidance of bacterial infections.


1. Collins F. Cystic fibrosis: molecular biology and therapeutic implications. Science. 1992;256:774-779.

2. Farrell PM, Fost N. Prenatal screening for cystic fibrosis: where are we now? J Pediatr. 2002;141:758-763.

3. Konstan MW, Butler SM, Wohl MEB, et al. Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis. J Pediatr. 2003;142:624-630.

4. Ratjen F, Doring G. Cystic fibrosis. Lancet. 2003;361: 681-689.

5. Amin R, Ratjen F. Cystic fibrosis: a review of pulmonary and nutritional therapies. Adv Pediatr. 2008;55:99-122.

6. McNally P. Cystic fibrosis. In: Florin TA, Ludwig S, eds. Netter’s Pediatrics. Philadelphia: Saunders Elsevier; 2011.