Porphyria Due To Ala Dehydratase Deficiency

Porphyria of doss or deficiency of delta-aminolevulinic acid dehydratase (DALAD) is an extremely rare form of acute hepatic porphyria (see this term) characterized by neuro-visceral attacks without cutaneous manifestations.

Epidemiology

To date, fewer than 10 cases have been described in the literature.

Clinical description

The disease occurs in children. Patients suffer acute neuro-visceral attacks, which persist for several weeks and manifest as intense abdominal pain, and neurological and psychological symptoms.

Etiology

Porphyria of Doss is caused by a deficiency of delta-aminolevulinic acid dehydratase (ALA-D, the second enzyme in the heme biosynthesis pathway) that leads to an accumulation of the precursors of porphyrins in the liver (delta-aminolevulinic acid, ALA). The enzyme deficiency is caused by mutations in the ALAD gene coded for ALA-D (to date, 9 mutations are known and expressed). Patients are most often composite heterozygous and transmission is autosomal recessive.

Diagnostic methods

The observation of urine that is pink or red after exposure to light evokes the diagnosis of the disease. Diagnosis is based on evidence of a massive accumulation of ALA in blood and urine. A definitive diagnosis is dependent on the identification of a causal mutation of the ALAD gene.

Genetic counseling

Genetic counseling should be offered to patients and families to identify individuals susceptible to developing or transmitting the disease, and to advise on measures to reduce the risk of attacks.

Management and treatment

When an acute attack is confirmed, urgent treatment with an injection of human hemin and/or perfusion of carbohydrates is required.

Prognosis

In some patients attacks may be recurrent and incapacitating, and sometimes fatal. They can, in some cases, cause motor paralysis. The disease is often progressive.