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Porphyria due to ALA dehydratase deficiency
A rare acute hepatic porphyria characterized by neurovisceral attacks without skin symptoms.
ORPHA:100924
Fewer than a dozen cases have been reported in the literature to date.
The disease is reported among children. Patients suffer acute neuro-visceral episodes that can last several weeks, manifesting as intense abdominal pain, neurological disorders and psychological disturbances.
Doss porphyria is due to a deficiency in delta aminolevulinic acid dehydratase (ALAD, the second enzyme in the heme biosynthesis pathway), which leads to an accumulation of porphyrin precursors (delta aminolevulinic acid, ALA) in the liver. The enzyme deficiency is due to mutations in the ALAD gene (NM_000031) coding for ALAD (to date, 9 mutations known and expressed). Patients most often have a compound heterozygosity. The transmission pattern is autosomal recessive.
The diagnosis is made on the basis of massive accumulation of ALA in the urine, with no increase in PBG. Diagnosis is based on the identification of a causal mutation in the ALAD gene.
Differential diagnosis should consider acute hepatic porphyria (in acute attack situations), type I tyrosinemia, and lead poisoning.
Prenatal diagnosis is theoretically possible in families at risk, but is not offered.
Genetic counseling is recommended to patients and families to identify individuals at risk of developing or transmitting the disease, and to advise them on measures to take to reduce the risk of an episode It should also be offered to at-risk couples (both individuals are carriers of a heterozygous pathogenic variant) informing them that there is a 25% risk of having an affected child at each pregnancy.
Administration of human hemin is of limited effectiveness in acute episode as is liver transplantation. In 2020, treatment with weekly blood transfusions and hydroxyurea was successfully attempted.
In some patients, acute attacks are recurrent and disabling, sometimes fatal. In some cases, they can lead to severe paralysis. The disease is often progressive.
Last update: March 2024 - Expert reviewer(s): Dr Neila TALBI | MetabERN*
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