Hyperplasia of pulmonary arterial media in infantile familial pulmonary hypertension associated with severe metabolic acidosis.

Abstract

Two female siblings, offspring of consanguinous parents, died at 10 and 12 wk of age following short illnesses characterized clinically by hypoxia and severe metabolic acidosis. Cardiac catheterization confirmed severe pulmonary hypertension in the second infant, who survived 6 wk after onset of symptoms and 4 wk after admission to hospital; extensive investigations failed to identify any inborn metabolic error. At autopsy, small pulmonary arteries/arterioles in both cases showed marked medial thickening due to smooth muscle hyperplasia; concentric intimal fibrosis was present focally in the older infant. Compared morphometrically with small pulmonary arteries in 20 infantile controls who died of Reye's syndrome (n = 8), a Reye's-like illness (n = 5) or an identified metabolic error associated with metabolic acidosis (n = 7), intraacinar pulmonary arteries in both cases, were significantly more numerous and had a significantly greater relative medial thickness. We suggest that an autosomal recessive gene caused or potentiated the pulmonary medial hyperplasia. The latter finding, compared with medial hypertrophy, is rarely described as the morphologic basis of pulmonary hypertension, and its occurrence may be restricted to early infancy. In this family, the relationship between hypertensive pulmonary arteriopathy and severe metabolic acidosis remains speculative.