Age: 18
Gender: Female
Occupation: Student
Working diagnosis: Left ventricular outflow tract obstruction and DiGeorge syndrome
HISTORY
The patient was the product of a normal pregnancy delivered at term. She initially had symptoms of heart failure on day 10 of life. She was found to have nearly complete aortic arch interruption, a VSD, and an ASD. Before a planned operative repair, she was noted to have hypocalcemia, which was corrected. Otherwise, she underwent repair of the aortic arch, VSD closure, and ASD closure and had no operative complications. Thereafter, she grew normally.
At 10 years of age the patient again developed heart failure symptoms. She was diagnosed with severe aortic valve stenosis, and a balloon valvotomy was attempted. During that hospitalization, however, she developed a severe systemic infection with severe splenomegaly and hepatomegaly. This was eventually diagnosed as a cytomegalovirus infection. Her aortic stenosis was not relieved after the balloon valvotomy, so she was considered for operative replacement of her aortic valve. She developed a transfusion reaction during a platelet transfusion that was being administered prophylactically for thrombocytopenia prior to a diagnostic angiogram. The patient eventually had replacement of her aortic valve with a 21-mm St. Jude prosthesis. Notably, several large mediastinal lymph nodes were removed during this surgery.
The patient did well initially after her aortic valve replacement, and cardiology follow-up visits were unremarkable. She was eventually diagnosed with selective IgA deficiency and treatment was initiated with monthly IVIG infusion. In late adolescence, however, she began to feel increasingly tired. She presented at 18 years of age with increasing fatigue and reduced exercise tolerance over the prior 6 months.
Comments: Cardiac anomalies commonly associated with DiGeorge syndrome include tetralogy of Fallot, pulmonary atresia/VSD, truncus arteriosus, and interrupted aortic arch.
Hypocalcemia in DiGeorge syndrome occurs secondary to absent parathyroid function. The term partial DiGeorge syndrome is applied when infants have impaired rather than absent parathyroid or thymus function, as in this case.
Patients with DiGeorge syndrome manifest a deficiency in cell-mediated immunity related to thymic hypoplasia. Susceptibility to infection is variable. Disorders of humoral immunity can also occur.
Some patients with DiGeorge syndrome produce autoantibodies to red cells, white cells, and platelets.
Fatigue is a very nonspecific symptom at any age, and late adolescence can cause psychosocial problems that can be difficult to decipher against the background of complex congenital heart disease. Further, DiGeorge patients are at risk for depression and schizophrenia. Still, a hemodynamic cause of deterioration must be sought.
CURRENT SYMPTOMS
The patient had exertional fatigue. She denied dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. She did not have intolerance to heat or cold, or constipation. Her menstrual cycles were regular but generally heavy. She noted that it had been very difficult to keep her INR in the therapeutic range. She also admitted that she was ambivalent about anticoagulation, as she was prohibited from some activities because of fear of injury and bleeding.
NYHA class: I–II
Comments: There were no typical symptoms of thyroid disease to explain her fatigue, but thyroid disease should be properly excluded by laboratory testing. Heavy menses may be associated with iron deficiency anemia, which may cause fatigue or exacerbate cardiac causes of fatigue. Selective IgA deficiency is associated with malabsorption and is another potential cause of iron deficiency anemia. Malabsorption likely contributes to difficulty in controlling oral anticoagulation and results in a need for higher warfarin doses. Noncompliance certainly needs to be considered, especially in teenagers and young adults with chronic disease who may rebel against the constraints placed on them. Compliance could be increased with home INR monitoring and education.
CURRENT MEDICATIONS
Trimethoprim/sulfamethoxazole, regular strength, orally twice daily
IVIG Polygam, every 5 weeks
Hydrocortisone prior to IVIG administration
Coumadin 9.5 mg daily (target INR 2.5–3.5)
Subacute bacterial endocarditis prophylaxis
Comments: Trimethoprim/sulfamethoxazole is administered prophylactically in this patient secondary to her reduced CD4 cell count. IVIG and steroids are useful in the treatment of autoantibodies to red cells, white cells, and platelets. This also provides treatment for deficiency of immunoglobulin, which this patient has demonstrated.
PHYSICAL EXAMINATION
BP 100/70 mm Hg (arm), 100/70 mm Hg (leg); HR 80 bpm; oxygen saturation 100%
Height 151 cm, weight 39 kg, BSA 1.28 m 2
Head and neck: Long, narrow face with a pointed chin, narrow palpebral fissures, and small ears with overfolding of the superior helix
Surgical scars: Sternotomy
Neck veins: Normal
Lungs/chest: Decreased air entry in the right lung base
Heart: There was a regular rhythm, a 2+ LV impulse, a crescendo-decrescendo murmur heard best at the right upper sternal margin, a crisp, metallic A2, and a suprasternal thrill. The carotid upstroke was delayed.
Abdomen: Marked hepatosplenomegaly was present.
Extremities: There was no radiofemoral delay; no cyanosis, clubbing, or edema.
PERTINENT NEGATIVES
She was not pale.
Comments: The patient’s height and weight are less than the third percentile when plotted on standard growth curves. Patients with DiGeorge syndrome commonly have short stature. This may be related to growth hormone deficiency or hypothyroidism, both of which have been associated with the syndrome. Poor growth is also seen in children with immunoglobulin deficiency.
Several “typical” facial features have been described in patients with DiGeorge or velocardiofacial syndrome. These include a small mandible, long face, large nose, narrow palpebral fissures, abnormal ear folding, and a flat malar region. However, the features described are subtle, and two separate studies have demonstrated an inability to predict whether a patient has the syndrome based on facial features.
The cardiac exam is consistent with severe aortic valve stenosis. There was no radiofemoral delay to suggest significant coarctation. She did not appear anemic.
LABORATORY DATA
| Hemoglobin | 11.3 g/dL (11.5–15.0) |
| Hematocrit/PCV | 33.8% (36–46) |
| MCV | 73 fL (83–99) |
| Platelet count | 106 × 10 9 /L (150–400) |
| Leukocyte count | 2.0 × 10 9 /L (3.5–10.5) |
| Sodium | 139 mmol/L (134–145) |
| Potassium | 3.8 mmol/L (3.5–5.2) |
| Creatinine | 0.7 mg/dL (0.6–1.2) |
Comments: A mild pancytopenia is present, which may be secondary to autoantibodies to red cells, white cells, and platelets. Iron deficiency is possible given the microcytic picture. The degree of anemia is unlikely to be the cause of her fatigue.
OTHER RELEVANT LAB RESULTS
| TSH | 4.0 mIU/L (0.3–5) |
| Bio-Intact PTH (1-84) | <4.0 pg/mL (10–55) |
| Calcium | 7.7 mg/dL (9.1–10.3) |
| Albumin | 4.6 g/dL (3.5–5.0) |
| INR | 1.9 |
| IgA | 2 mg/dL (55–377) |
| IgM | 19 mg/dL (56–242) |
| IgG | 1310 mg/dL (724–1611) |
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