Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency.
Molecular characterization, by digital PCR analysis of four HMBS gene mutations affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients with Acute Intermittent Porphyria (AIP).
A modified spectrophotometric assay for porphobilinogen deaminase: its application in the detection of both carriers and patients with acute intermittent porphyria.
Detection of a R173W mutation in the porphobilinogen deaminase gene in the Nova Scotian "foreign Protestant" population with acute intermittent porphyria: a founder effect.
Three enzymic changes have now been identified in patients with acute intermittent porphyria; a high level of delta-aminolevulinate synthase activity; a low level of uroporphyrinogen I synthase activity; and a deficiency of steroid Delta(4)-5alpha reductase activity.
May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population.
A single base insertion of C in exon 15 of the porphobilinogen deaminase (PBG-D) gene was observed in a patient with acute intermittent porphyria (AIP) by polymerase chain reaction (PCR)-direct sequencing analysis.
Previous haplotype analysis combined with genealogical data suggested a common origin of the PBGD gene mutation in the AIP families originating from northern Sweden (Lappland), where the highest prevalence of the disease (1 in 1500) is observed.
An inherited deficiency of porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] in humans is responsible for the autosomal dominant disease acute intermittent porphyria.
Three splicing defects (IVS1+3G-->T, 86A-->T, IVS13-2A-->G), an insertion (416insCA), and two missense mutations (664G-->A and 833T-->G) in the porphobilinogen deaminase (PBGD) gene were identified in six unrelated Finnish patients with acute intermittent porphyria (AIP).
To investigate the dramatically different manifestations, knock-in mice with human HD-AIP missense mutations c.500G>A (p.Arg167Glu) or c.518_519GC>AG (p.Arg173Glu), designated R167Q or R173Q mice, respectively, were generated and compared with the previously established T1/T2 mice with ~30% residual HMBS activity and the heterozygous AIP phenotype.
A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD).
The three-dimensional structures of mutants of porphobilinogen deaminase: toward an understanding of the structural basis of acute intermittent porphyria.
Molecular analysis of the hydroxymethylbilane synthase (HMBS) gene in Italian patients with acute intermittent porphyria: report of four novel mutations.