Enzymatic Defect in a Child With Hereditary Hepatic Porphyria Due to Homozygous δ-Aminolevulinic Acid Dehydratase Deficiency: Immunochemical Studies

Immunochemical studies of the enzyme defect in the first reported child with acute hepatic porphyria due to homozygous δ-aminolevulinic acid dehydratase deficiency are described. This enzyme activity was markedly decreased (approximately 2% of the normal control level) in the proband, a 3-year-old boy, and intermediately decreased (23% to 57%) in both parents, in both grandfathers, and in a sister, but it was normal in two siblings and in both grandmothers. In contrast to the profound decrease in δ-aminolevulinic acid dehydratase activity, the immunoreactive enzyme protein in the child's erythrocytes was decreased to only 28% of the normal control level, suggesting the presence of positive cross-reactive material. In other family members with abnormally decreased δ-aminolevulinic acid dehydratase activity, and in the proband immediately after transfusion of normal RBCs, the positive cross-reactive material was not detectable. The immunochemical and enzyme activity data support the idea that δ-aminolevulinic acid dehydratase deficiency in this porphyric child is associated with the production of a catalytically abnormal enzyme protein.