Abstract 183

Aim - To describe two siblings with a severe condition of as yet unclear pathogenesis to stimulate the recognition and report of similar patients by other centres.

Case reports - Parents from a small village, healthy, with normal blood cell counts. Both pregnancies complicated by preeclampsia; both siblings born SGA with transitory neonatal RDS but discharged in good conditions. Sibling 1, a girl, presenting at age 3 mo with tachypnoea, poor feeding and hypotonia. Polycythemia (Hb 232 g/L, Ec 7,94 G/ml), pulmonary hypertension (45 - 75 mmHg, not responding to PGs or NO) and increased plasma EPO levels (repeatedly over 500 U/L; normal, <30) were found; tcpO2 was normal. Partial exchange transfusion was uneffective. The infant died with intractable heart failure at age 4 mo. Autopsy findings: no tumor, cardiovascular malformation, or pulmonary emboli; histology of pulmonary arteries unremarkable, but intrapulmonary perivascular hematopoietic tissue was found. Sibling 2, a boy, presented with similar clinical findings at age 2 mo; polycythemia (Hb 194 g/l, Ec 6,72 G/ml), repeatedly increased EPO levels (112-525 U/l), pulmonary hypertension (70-100 mm Hg on EchoCg), and tendency to hypoglycemia were found. TcpO2 was normal. Hemoglobin structure and 2,3-DPG levels were normal. Correction of polycythemia by venipuncture had no effect on pulmonary hypertension.

Discussion - EPO elevation was not caused by hypoxia, cardiovascular malformation of fistula, or tumor. Familial erythrocytosis, a benign disorder with minimal clinical consequences, is unlikely. Idiopathic pulmonary hypertension does usually not produce increased EPO and polycythemia, and histological changes were lacking. Conversely, the autoptic finding of intrapulmonary hematopoiesis in sibling 1 is unusual.

Conclusion and speculation - The pathogenesis of this syndrome, which resembles a hypoxic response, remains obscure. A genetic defect in some regulatory element, or in the oxygen sensor system, might be the cause. Preeclampsia during both pregnancies may indicate that the defect is expressed also in placental tissue.