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

CASE 6-2

Seven-Month-Old Boy



A 7-month-old white male was admitted for evaluation of failure to thrive. The patient was a former twin B who was born at 37 weeks gestation. The mother’s pregnancy was uncomplicated and the patient had been doing well until 3 months of age. At that time the patient had bilateral inguinal hernia repair. Since then his parents noticed that he has not been gaining weight. His stools were loose, foul smelling, and occurred 6-7 times per day. There was no history of fevers or vomiting and his appetite was described as greater than his twin brother who was thriving.


The boy was a former 37-week twin of an uncomplicated pregnancy, labor, and delivery. Mother denies having any sexually transmitted diseases. He takes no medications and has no allergies. He received his immunizations during an office visit at 6 months of age. Family history was remarkable for a father with diabetes. The child lived with his mother, father, his twin, and 3-year-old sister. Both siblings were healthy. Developmentally, the child was unable to sit unassisted, had not rolled over, and still had some head lag on repeated testing.


T 37.2°C; HR 110 bpm; RR 20/min; BP 78/50 mmHg

Height <5th percentile and Weight <5th percentile

In general, the child was emaciated but interactive. His head was normocephalic and pupils were equally round and reactive to light. The sclera was anicteric. The tympanic membranes were normal in appearance and mobility. The neck was supple with free range of motion. There was no lymph node enlargement or palpable masses. The chest was clear bilaterally. There were no murmurs, gallops, or rubs on cardiovascular examination. The abdomen was soft, nontender, and nondistended with positive bowel sounds. There was no hepatosplenomegaly or masses. The genitalia were normal. There was clinodactyly. Neurologic examination showed global weakness and head lag. The skin had a fine erythematous macular rash over the extremities.


Complete blood count revealed the following: hemoglobin, 2.2 g/dL; platelets, 180 000/mm3; and 1000 white blood cells/mm3 (2% band forms, 8% segmented neutrophils, 81% lymphocytes, and 9% monocytes). Serum electrolytes were as follows: sodium, 138 mEq/L; potassium, 3.6 mEq/L; chloride, 103 mEq/L; and bicarbonate, 22 mEq/L. The serum albumin was 4.2 mg/dL. Prothrombin and partial thromboplastin times were 12.5 and 31.0 seconds, respectively. A sweat test was normal.


The patient was evaluated for malabsorptive stool pattern. He was shown to have increased fecal fat and evidence of pancreatic insufficiency. This finding in conjunction with findings on physical examination and complete blood count suggested a diagnosis.



The differential diagnosis of growth failure due to malabsorption is a long one. Once the type of malabsorption is narrowed down to exocrine pancreatic dysfunction then the cause may be narrowed to hereditary and acquired causes. The hereditary causes include cystic fibrosis, Shwachman-Diamond syndrome, Johnson Rizzald syndrome, Pearson’s Pancreatitis and Bone Marrow syndrome, and isolated enzyme deficiency. Acquired causes result from chronic pancreatic and surgical causes.

Other causes of malabsorption are many and include defects in the luminal phase, the mucosal phase, or the transport phase of absorption and digestion. Table 6-5 shows tests that may be used to evaluate the different forms of malabsorption.

TABLE 6-5. Diagnostic studies in the evaluation of malabsorption.

Initial Screening Studies

Stool examination for occult blood, leukocytes, reducing substances, and pH

Stool examination for Clostridium difficile toxin, ova, and parasites

Stool cultures for infectious and viral pathogens

Serum electrolytes, albumin, and total protein

Urinalysis and culture

Quantitative and Qualitative Tests for Malabsorption

Breath H2 studies

D-Xylose absorption for mucosal function

Fecal fat studies

Serum iron, vitamin B12 folate

Specific Diagnostic Studies

Sweat chloride test

Small intestinal biopsy for histology and mucosal enzyme

Contrast radiographic studies: upper gastrointestinal series with small-bowel follow-through and/or barium enema

Provocative pancreatic secretion testing

Ultrasound for biliary tree anomalies

Endoscopic retrograde cholangiopancreatograph (ERCP) for selective evaluation of biliary or pancreatic ducts

Source: Adapted from: Hill ID. Disorders of digestion and absorption. In: Rudolph CD, Rudolph AM, eds. Rudolph’s Pediatrics, 21st ed. New York: McGraw-Hill; 2003.


The presence of neutropenia and a skeletal abnormality (clinodactyly) in conjunction with pancreatic insufficiency suggested the diagnosis of Shwachman syndrome. The diagnosis is Shwachman-Diamond syndrome, the second most common cause of hereditary pancreatic insufficiency; cystic fibrosis is the most common cause. The stool pattern and growth pattern is similar to cystic fibrosis but patients with Shwachman syndrome will have other features. These are often short stature with a normal growth pattern. Skeletal deformities have been noted in the thorax and fingers. Some children will also manifest bone marrow dysfunction, more often causing neutropenia and frequent infections, but also anemia and thrombocytopenia.


Shwachman-Diamond syndrome, an autosomal recessive disorder, results in exocrine pancreatic insufficiency, skeletal abnormalities (e.g., cinodactyly, syndactyly, supernumerary metatarsals), and bone marrow dysfunction, the latter of which predisposes to myelodysplastic syndrome and acute myeloid leukemia. The exact prevalence is unknown but estimates based on comparison cystic fibrosis data suggest a prevalence of approximately 1 per 75 000. There does not appear to be a racial or ethnic predisposition but males are more commonly affected than females.

Affected children have some degree of pancreatic insufficiency early in life. Thus, the diagnosis is typically suspected within the first year of life. The typical presentation includes malabsorption, steatorrhea, and failure to thrive. Symptoms related to deficiencies in fat-soluble vitamins (i.e., A, D, E, K) may also be present. Neutrophil migration defects and neutropenia predispose to recurrent bacterial infections, most commonly sino-pulmonary infections and, occasionally, skin and soft tissue infections and osteomyelitis. Bone marrow failure leads to anemia, easy bruising, and recurrent epistaxis. Defects in tooth enamel predispose to dental caries. Most patients have mild cognitive impairment. Children with Shwachman-Diamond syndrome are also at higher risk of hematologic malignancies.


The diagnostic approach is similar to that of a child with cystic fibrosis; yet the sweat test is normal but some of the other distinguishing features may be present. There is no single laboratory marker. Shwachman-Diamond syndrome is a clinical pheno-type with central features of pancreatitis and bone marrow dysfunction. Other causes of pancreatic dysfunction must be eliminated.

Sweat test. The sweat test, performed to exclude cystic fibrosis as a cause of pancreatic insufficiency, reveals normal sweat chloride levels.

Complete blood count. The complete blood count typically reveals persistent or cyclic neutropenia, anemia, and, occasionally, thrombocytopenia.

Serum electrolytes. Serum bicarbonate may be low.

Hepatic transaminases. Hypoalbuminemia occurs as a consequence of malabsorption. Alanine and aspartate aminotransferases may be mildly elevated.

Fecal fat measurement. A 72-hour fecal fat measurement demonstrates an increase in fecal lipids and fatty acids, though the absence of steatorrhea does not exclude the possibility of Shwachman-Diamond syndrome.

Serum immunoglobulins. IgA and IgG levels may be low.

Bone marrow aspirate. Bone marrow may show hypoplasia with fibrosis. It may also reveal hematologic malignancy. Patients who have their first symptoms younger than 3 months of age, and those with low hematologic parameters at diagnosis and during follow-up are at highest risk for developing hematologic complications, both malignant and nonmalignant.

Radiologic evaluation. A skeletal survey may reveal osteopenia, metaphyseal chondrodysplasia (e.g., metaphyseal widening), costochondral thickening, and abnormal tubulation of the long bones. Abdominal MRI has been used to identify fatty replacement of the pancreas.


Treatment includes enzyme replacement, nutritional support, infection prevention, and vigilance to detect hematologic malignancies. Careful attention should be paid to vitamin therapy of the fat-soluble vitamins and careful treatment for infections and other hematologic manifestations. The response to treatment is good in most cases. The patients may be prone to infections due to the neutropenia. Some patients may also develop acute myelogenous leukemia (AML).


1. Mark DR, Forstner GG, Wilchanski M, et al. Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression. Gastroenterology. 1996;111: 1593-1602.

2. Baldassano R, Liacouras C. Chronic diarrhea: a practical approach for the pediatrician. Pediatr Clin North Amer. 1991;38:667-674.

3. Rothbaum R, Perrault J, Vlachos A, et al. Shwachman-Diamond syndrome: report from an international conference. J Pediatr. 2002;14:266-270.

4. Ruggiero A, Molinari F, Coccia P, et al. MRI findings in Shwachman-Diamond syndrome. Pediatr Blood Cancer. 2008;50:352-354.

5. Donadieu J, Fenneteau O, Beaupain B, et al. Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome. Haematologica. 2012;97: 1312-1319.