IllnessPorphyria, differential diagnosis

NGS +

[Sanger]

The porphyria group consists of hereditary metabolic diseases that lead to enzyme defects in the synthesis of the red blood pigment heme as a result of pathogenic variants in different genes. Depending on the enzyme affected, various intermediate products accumulate which are responsible for the characteristic symptoms of the various forms of porphyrias. Blood, stool and/or urine analyses of total porphyrins and the intermediate products of heme synthesis can be used to make a suspected diagnosis, which can be confirmed by genetic testing.

Porphyrias are divided into two forms according to clinical symptoms: On the one hand, “acute porphyrias” (ALA dehydrase deficiency porphyria, acute intermittent porphyria, porphyria variegata, hereditary coproporphyria), in which acute abdominal symptoms (colicky abdominal pain, vomiting, constipation) occur in episodes together with neurological deficits (seizures, paresis), neurovegetative symptoms (tachycardia, hypertension) and psychiatric abnormalities (so-called neuro-visceral form). Reddish urine is typical, but only during acute attacks. The most common acute porphyria is acute intermittent porphyria (AIP), which can lead to coma and tetraplegia in severe cases. On the other hand, there are the so-called “non-acute porphyrias” (porphyria cutanea tarda, hepatoerythropoietic porphyria, congenital erythropoietic porphyria, erythropoietic protoporphyria, X-linked dominant protoporphyria), which usually involve the skin (photodermatoses, blistering, pigment disorders, hypersensitivity (pain, burning, itching, redness, especially after sun exposure). In two forms of porphyrias, hereditary coproporphyria and porphyria variegata, both acute neurovisceral and chronic cutaneous symptoms can occur.

Porphyrias can be further subdivided according to the main site of formation of the intermediate products of haem synthesis: hepatic porphyrias (main site of formation in the liver) and erythropoietic porphyrias (main site of formation in the bone marrow).

In the case of porphyria, the genes coding for the enzymes of heme synthesis are examined so that all forms of porphyria and genetic differential diagnoses (e.g. hemochromatosis, UV hypersensitivity) are covered. The various forms of porphyrias are inherited differently: most forms are inherited autosomal-dominantly with reduced penetrance. Autosomal recessive (e.g. variants in ALAD) and X-linked inheritance (e.g. variants in ALAS2) are also possible. If a genetic diagnosis has been confirmed in the family, predictive tests for the gene variant(s) can be carried out on relatives.

https://www.ncbi.nlm.nih.gov/books/NBK1193/

https://www.ncbi.nlm.nih.gov/books/NBK143129/

https://www.ncbi.nlm.nih.gov/books/NBK121283/

https://flexikon.doccheck.com/de/Porphyrie

• Alias: Inherited defects in the biosynthesis of heme
• Allelic: Alzheimer disease, susceptibility to (HFE)
• Allelic: Anemia, XL, with/-out neutropenia and/or platelet abnormalities (GATA1)
• Allelic: Anemia, sideroblastic, 1 (ALAS2)
• Allelic: Hemochromatosis (HFE)
• Allelic: Lead poisoning, susceptibility to (ALAD)
• Allelic: Leukemia, megakaryoblastic, with/-out Down syndrome, somatic (GATA1)
• Allelic: Microvascular complications of diabetes 7 (HFE)
• Allelic: Thrombocytopenia with beta-thalassemia, XL (GATA1)
• Allelic: Transferrin serum level QTL2 (HFE)
• Coproporphyria (CPOX)
• Ferrochelatase deficiency; Haem-synthetase deficiency (FECH)
• Harderoporphyria (CPOX)
• Porphyria cutanea tarda (UROD)
• Porphyria cutanea tarda, susceptibility to (HFE)
• Porphyria variegata (PPOX)
• Porphyria variegata, susceptibility to (HFE)
• Porphyria, acute hepatic (ALAD)
• Porphyria, acute intermittent (HMBS)
• Porphyria, acute intermittent, nonerythroid variant (HMBS)
• Porphyria, congenital erythropoietic (UROS)
• Porphyria, hepatoerythropoietic (UROD)
• Protoporphyria, erythropoietic, 1 (FECH)
• Protoporphyria, erythropoietic, 2 (CLPX)
• Protoporphyria, erythropoietic, XL (ALAS2)
• Rothmund-Thomson syndrome, type 1 (ANAPC1)
• Rothmund-Thomson syndrome, type 2 (RECQLA4)
• Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)