ADP is an autosomal recessive disorder that is a member of a family of disorders referred to as the porphyrias. Each disease in this family results from deficiencies in a specific enzyme involved in the biosynthesis of heme (also called the porphyrin pathway). The term porphyria is derived from the Greek term porphura which means "purple pigment" in reference to the coloration of body fluids in patients suffereing from a porphyria. The porphyrias are classified on the basis of the tissue that is the predominant site of accumulation of metabolic intermediates. These classifications are "hepatic" or "erythroid". Each disease is also further characterized as being acute or cutaneous dependent upon the major clinical features of the disease. ADP is an autosomal recessive disorder that results from defects in δ-aminolevulinic acid dehydratase, also called porphobilinogen synthase (PBG synthase). ADP is classified as an acute hepatic porphyria.
The ALA dehydratase gene (symbol: ALAD) is located on chromosome 9q33.1 spanning 16 kb and encompassing 16 exons encoding a 330 amino acid protein. The ALAD gene is subject to alternative splicing generating two mRNAs, one is erythroid cell-specific and the other is expressed in all tissues and is referred to as the house-keeping form. The house-keeping transcript contains exon 1A and then exons 2 through 12 while the erythroid-specific transcript contains exon 1B and then exons 2 through 12. Functional ALA dehydratase is complex composed of eight identical subunits derived from the ALAD encoded mRNAs. Very few cases of ADP have been reported and in those few individuals missense and frameshift mutations were identified in the ALAD gene.
The clinical manifestations of ADP are heterogeneous and somewhat similar to those seen in patients with acute intermittent porphyria, AIP. Common symptoms include abdominal pain and neuropathy. The symptoms of ADP are due to the accumulation and urinary excretion of large amounts of δ-aminolevulinic acid, ALA. Acute attacks of ADP are believed to occur in association with overexpression of δ-aminolevulinic acid synthase 1 (ALAS1) in the liver. ALAS is the rate-limiting enzyme of heme biosynthesis. ADP heterozygotes are at increased risk of acute attacks of porphyria if exposed to certain compounds such as iron, trichloroethylene, and styrene that have adverse effects on the activity of ALAD.