Enzymatic defect in a child with hereditary hepatic porphyria due to homozygous delta-aminolevulinic acid dehydratase deficiency: immunochemical studies.
Immunochemical studies of the enzyme defect in the first reported child with acute hepatic porphyria due to homozygous delta-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 delta-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 delta-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 delta-aminolevulinic acid dehydratase deficiency in this porphyric child is associated with the production of a catalytically abnormal enzyme protein.
Rockefeller University Hospital, New York, NY 10021-6399.
H
H
Fujita
S
S
Sassa
J
J
Lundgren
L
L
Holmberg
S
S
Thunell
A
A
Kappas
D001798:Blood Proteins / Q000276:immunology; D001803:Blood Transfusion; D002675:Child, Preschool; D003429:Cross Reactions; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D008297:Male; D000623:Porphobilinogen Synthase / Q000172:deficiency* / Q000378:metabolism; D011164:Porphyrias / Q000209:etiology / Q000378:metabolism*; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D001798:Blood Proteins; D011163:Hydroxymethylbilane Synthase; D014575:Uroporphyrinogen Decarboxylase; D000623:Porphobilinogen Synthase