What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)?
ADP is an autosomal recessive disorder caused by mutations in the ALAD gene. These mutations reduce the function of an enzyme called δ-aminolevulinic acid dehydratase, which is needed for heme production. Without enough of this enzyme, the body can’t properly convert the chemical δ-aminolevulinic acid (ALA) into porphobilinogen, an essential step in making heme. ALAD is an extremely rare form of porphyria with around 12 cases reported worldwide. ADP is more severe than the other acute porphyrias and can present in childhood. Additionally, the bone marrow is an important source of overproduction of heme pathway intermediates.
How is δ-Aminolevulinic Acid Dehydratase Porphyria diagnosed?
Acute porphyrias are diagnosed using biochemical testing, starting with a urine test to measure porphyrin precursors and porphyrins. This is best done during symptoms, because results may be normal between attacks. A spot urine sample rather than a 24-hour urine sample is recommended. The levels of urinary ALA and PBG during an attack are expected to be markedly elevated. Porphyrins are also elevated, but this finding is not specific for an acute porphyria. Additional blood, urine and stool tests are needed to help determine the specific type of acute porphyria. In ADP, urine ALA and coproporphyrin III are elevated. Additional red cell zinc protoporphyrin is increased.
Genetic testing can confirm the specific type of porphyria, but it does not replace biochemical testing, which is needed to determine whether the disease might be active and causing symptoms.
Genetic testing is essential for establishing a diagnosis of ADP.
Family members of individuals diagnosed with acute porphyria may benefit from testing to see if they have inherited the same mutation. Decisions regarding such testing should consider personal preferences with guidance from a provider with expertise in the porphyrias or genetics.
What are treatments for δ-Aminolevulinic Acid Dehydratase Porphyria?
Due to its extreme rarity, optimal management of ADP is unknown. Hemin has been effective in a number of people with ADP. Hemin and red cell transfusion was effective in a single case. There is very limited experience with givosiran for this disease. It was not effective in a single case.
How is δ-Aminolevulinic Acid Dehydratase Porphyria Inherited?
ADP is an autosomal recessive condition. Autosomal means that the defect is not on the chromosomes that determine sex, and recessive means that both copies of the gene are mutated. The gene that causes ADP is called ALAD.