Three new cases of the world's rarest form of infantile porphyria identified

Hepatic porphyrias are a subject orphan genetic diseases that affect the synthesis of hemoglobin and other hemoproteins, whose most common symptom is severe abdominal pain, although in the most serious cases they can cause severe neurological disorders. Among them, ALA dehydratase deficiency (ADP) porphyria is the rarest and most severe form of porphyria affecting early childhood. To date, only 10 cases have been reported in males.

A study led by the Cima of Navarra, in partnership European researchers, has identified three new cases of this disease, the first of which in a girl. "This work core topic information core topic understanding the genetic and environmental mechanisms involved in this ultra-rare porphyria and its relationship with heavy metal toxicity. Specifically, we have described five cases of severe lead poisoning in adults, which clinically mimic the childhood disease," explains Dr. Antonio Fontanellas, researcher of the Hepatology: Porphyrias and Carcinogenesisgroup Cima and director work. 

Susceptibility to lead poisoning

Although lead poisoning is becoming less common thanks to preventive measures and public awareness, accidental exposure still occurs. This metal can be found in old pipes, utensils and tableware, cosmetics, bullet casings, illegal liquors, adulterated opium, and some herbal supplements. Lead is easily absorbed and accumulates in the blood and other tissues, where it can cause damage even in small amounts.

Using an approach combines genetic and biochemical analyses with an innovative model for programs of study , the researchers identified new variants of the gene with different expression and biochemical behavior. The results reveal great molecular heterogeneity, which could explain the different susceptibility of some people to lead poisoning. "Due to its extreme rarity, each well-studied patient represents a unique opportunity to advance our understanding of this disease," the authors conclude.

The study, conducted within the framework area of Liver and Digestive Diseases (CIBEREHD) and in partnership area of Rare Diseases (CIBERER), was funded by the Carlos III Health Institute and the Mutua Madrileña Foundation. 

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●J Intern Med.2025Nov 21. doi: 10.1111/joim.70044.
New cases of δ-aminolevulinic acid dehydratase deficiency: Functional insights into gene variants using an innovative mouse liver model