We have studied 11 newborn infants of 8 families with a new lethal disease. The presenting finding was severe fetal growth retardation (mean ± SD gest. age 36.4 ± 2.6 wk, birth weight 1480 ± 400 g ie. -4.1± 0.5 SD). Apgar score was 7-10, cord pH was normal (n=4). By 24 h of age, mean pH was 7.00 ± 0.11, BE -24 ± 3.8, lactate 12.3± 8 mml/L, pyruvate 143 ± 75 μmol/L, lactate pyruvate ratio 96 ± 61. All infants had aminoaciduria, failed to thrive, and died either early (age 2-12 days, n=6) or in infancy (10-18 wk, n=5). The activity of complex I of the respiratory chain was decreased (n=4). Known etiologies of lactacidosis were excluded.

Autopsy revealed hemosiderosis of the liver in all cases. Serum ferritin was 1365-2400 μg/L (reference range 10-150), iron 15-17 μmol/L (8-30), transferrin 0.5-0.6 g/L, transferrin saturation 98-100% (n=2). In one case, desferrioxamine and apotransferrin infusions, followed by exchange transfusions, resulted in normal transferrin saturation, transient normalization of pH and clinical improvement. Immunoelectrophoresis and immunofixation of her and her parents' transferrin were normal.

Conclusion: This presumably genetic disease is distinct from other lactacidoses and neonatal hemochromatosis. Organ dysfunction may be due to the toxic effects of free iron.