Index of Suspicion

Case 1 Presentation

A 12-month-old girl who has trisomy 18 presents with 3 weeks of intermittent fever, emesis, and irritability, but no diarrhea, rash, lethargy, or seizure activity. In addition, she has lost nearly 300 g over the previous 3 months. Her medical history includes repair of tetralogy of Fallot, first-degree atrioventricular block, chronic lung disease, seizures, and gastroesophageal reflux. Medications include phenytoin and inhaled corticosteroids.

Physical examination reveals a small, irritable, dysmorphic child who has a temperature of 101.1°F (38.4°C) and blood pressure of 122/57 mm Hg. Height, weight, and head circumference are below the third percentile. There is a 3/6 systolic regurgitant murmur. Abdominal examination is limited due to pacemaker placement in the right upper quadrant, but the liver is palpated 3 cm below the costal margin and spleen at 2 cm. The remainder of the physical findings are normal.

CBC is normal except for a WBC count of 18.5×10³/mcL (18.5×10⁹/L) and platelet count of 806.0×10³/mcL (806.0×10⁹/L). Blood chemistry results, including a standard liver panel that includes concentrations of total protein and albumin, are normal. Urinalysis reveals mild proteinuria and hematuria, and the CSF is normal. Initial blood cultures grow Streptococcus viridans. The fever and bacteremia resolve with intravenous antibiotic therapy, but the hypertension and irritability persist.

Subsequently, her right thigh becomes swollen and tender. A radiograph reveals severe osteopenia and a femur fracture. A skeletal survey demonstrates diffuse osteopenia, as well as old pathologic fractures of both radii and ulnae and some ribs. Additional laboratory evaluation reveals mild hypothyroidism (thyroid-stimulating hormone of 11.2 mIU/mL, free thyroxine of 1.03 ng/mL [13.3 pmol/L]). Concentrations of parathyroid hormone, insulin-like growth factor, morning cortisol, dihydroxyvitamin D, 25-hydroxyvitamin D, calcium, ionized calcium, phosphorus, and alkaline phosphatase are normal. An imaging study reveals the underlying cause of …