1/7. Coexistence of discoid lupus erythematosus and porphyria cutanea tarda.A case of coexistent porphyria cutanea tarda and discoid lupus erythematosus is presented. Abnormal urinary porphyrins, the presence of liver fluorescence, chronic alcoholism, fatty metamorphosis of the liver and histologically typical LE with the demonstration of basement membrane fluorescence were present in the patient. awareness of the possible coexistence of these two conditions is of practical significance for the practicing dermatologist. The nature of the relationship between these conditions remains obscure. Is it coincidental or does it represent a common pathophysiological mechanism? Further work on this unique pair of diseases seems indicated.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/7. Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria.The properties of 9 delta-aminolevulinate dehydratase (ALAD) mutants from patients with ALAD porphyria (ADP) were examined by bacterial expression of their complementary DNAs and by enzymologic and immunologic assays. ALADs were expressed as glutathione-S-transferase (GST) fusion proteins in escherichia coli and purified by glutathione-affinity column chromatography. The GST-ALAD fusion proteins were recognized by anti-ALAD antibodies and were enzymatically active as ALAD. The enzymatic activities of 3 ALAD mutants, K59N, A274T, and V153M, were 69.9%, 19.3%, and 41.0% of that of the wild-type ALAD, respectively, whereas 6 mutants, G133R, K59N/G133R, F12L, R240W, V275M, and delTC, showed little activity (< 8%). These variations generally reflect the phenotype of ALAD in vivo in patients with ADP and indicate that GST-ALAD fusion protein is indeed useful for predicting of the phenotype of ALAD mutants. The location of F12L mutation in the enzyme's molecular structure indicates that its disturbance of the quaternary contact of the ALAD dimer appears to have a significant influence on the enzymatic activity. Mouse monoclonal antibodies to human ALAD were developed that specifically recognized a carboxy terminal portion of ALAD, or other regions in the enzyme. This study represents the first complete analysis of 9 mutants of ALAD identified in ADP and indicates the highly heterogeneous nature of mutations in this disorder.- - - - - - - - - - ranking = 5keywords = nature (Clic here for more details about this article) |
3/7. Congenital erythropoietic porphyria. A mild variant with low uroporphyrin I levels due to a missense mutation (A66V) encoding residual uroporphyrinogen III synthase activity.BACKGROUND AND DESIGN--Congenital erythropoietic porphyria, an inborn error of heme biosynthesis, results from the deficient activity of the enzyme uroporphyrinogen III synthase. The clinical manifestations in unrelated patients with this autosomal recessive disorder are remarkedly variable, ranging from mild cutaneous involvement to severe transfusion-dependent hemolytic anemia. Biochemical and molecular studies were undertaken to investigate the nature of the unusually mild phenotype in a 15-year-old boy with only cutaneous manifestations. RESULTS--The proband's levels of total porphyrins, urinary uroporphyrin I, and erythrocyte coproporphyrin I were elevated, but not as dramatically as in other patients with this porphyria. Interestingly, the erythrocyte uroporphyrinogen III synthase activity in the proband was about 21% of the normal mean, indicating the presence of significant residual activity. In cultured lymphoblasts from the proband, his father, and mother, the enzymatic activities were 10%, 70%, and 50% of the normal mean, respectively. Molecular analyses revealed that the proband was heteroallelic for two uroporphyrinogen III synthase missense mutations: the C73R allele inherited from his mother and the A66V allele transmitted by his father. The A66V allele encoded residual enzymatic activity in vitro while the C73R allele did not. CONCLUSIONS--The A66V allele accounted for the proband's low levels of porphyrin accumulation and mild clinical manifestations. Such genotype-phenotype correlations should provide understanding of the remarkable clinical variability in other patients with this inherited porphyria.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/7. delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote.delta-Aminolevulinate dehydratase deficient porphyria, a recently recognized inborn error of heme biosynthesis, results from the markedly deficient activity of the heme biosynthetic enzyme, delta-aminolevulinate dehydratase (ALA-D). The four homozygotes described to date with this disorder have remarkably distinct phenotypes, ranging from a severely affected infant with failure to thrive to an essentially asymptomatic 68-year-old male. To investigate the molecular nature of the lesions causing the severe infantile-onset form, total rna was isolated from cultured lymphoblasts of the affected homozygote, rna was reverse-transcribed to cDNA, and the 990-bp ALA-D-coding region was amplified by the PCR. Heterozygosity for an RsaI RFLP within the ALA-dehydratase-coding region permitted identification of the paternal and maternal mutant alleles prior to sequencing. The maternal mutation (designated G133R), a G-to-A transition of nucleotide 397, predicted a glycine-to-arginine substitution at residue 133 at the carboxyl end of the highly conserved zinc-binding site in the enzyme subunit. The G133R mutation created a PstI site and permitted the confirmation and rapid detection of this lesion in amplified genomic dna from maternal relatives. The paternal mutation, a G-to-A transition of nucleotide 823, predicted a valine-to-methionine substitution of residue 275 (designated V275M). This mutation was confirmed in genomic dna from family members by the competitive PCR technique. Both missense mutations, which occurred at CpG dinucleotides, resulted in the synthesis of enzyme subunits such that the activity of the homooctameric enzyme was markedly reduced, thereby causing the severe infantile-onset phenotype in the affected homozygote.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/7. Protoporphyrin (proto)-determined hepatopathy in a South African Jewish family.A detailed study of a Jewish erythrohepatic protoporphyria (EHP)-affected family with a sibship consisting of 2 brothers and a sister, all of whom manifested protodetermined hepatopathy which varied from relatively mild hepatic involvement in the sister to a fulminant fatal illness in the eldest brother. The nature and course of his illness as well as the autopsy findings are described in detail. This sibship is also unique in that the 2 brothers and biochemical evidence of a severe degree of G6PD deficiency, while the sister was shown to be a carrier.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
6/7. Varied psychiatric manifestations of acute intermittent porphyria.Acute Intermittent Porphyria (AIP) is an autosomal dominant metabolic disorder that has various psychiatric manifestations. This is a report of a case who had six brief psychotic episodes of varying nature within a 2-month period. The psychotic manifestations included catatonic stupor, hypomania, and delirium in different episodes. The management aspects of the case have been highlighted.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
7/7. Erythropoietic protoporphyria. Hepatic implications.The terminal stages of erythropoietic protoporphyria are recorded. The observations are related to the site of the fundamental lesion and the nature of the biochemical defect. The possibly ominous prognosis in this usually mild condition is emphasized. Apart from congenital porphyria, the porphyrias do not usually confer severe cutaneous lesions. These diseases present to dermatologists because of moderate photosensitivity and are not usually regarded as a risk to life. Dangerous central nervous system involvement may occur, however, in acute intermittent, variegate and hereditary coproporphyrias, while in acquired symptomatic porphyria severe underlying liver dysfunction may occur. Probably the most common familial photosensitizing porphyria is erythropoietic protoporphyria. Recently some deaths from severe liver involvement have been reported in this disease.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |