Porphyrias are inborn errors of
heme biosynthesis pathway that result in neurovisceral and/ or cutaneous manifestations which occur with episodic attacks, usually accompanied by a multisystemic involvement. Acute
hepatic porphyrias include
acute intermittent porphyria,
variegate porphyria,
hereditary coproporphyria, and
aminolevulinic acid dehydratase deficiency
porphyria. Acute
hepatic porphyrias may present with symptoms of an affected central, peripheral, and autonomic nervous system and are generally diagnosed in time of an acute neurovisceral attack. In children, clinical picture is more complicated and presents with neurological findings predominantly. First-line investigation should be the urinary
porphobilinogen and
aminolevulinic acid performance when
acute hepatic porphyria is clinically suspected. Comprehensive testing including urine
porphyrin separation, fluorescence scanning of diluted plasma at neutral pH, evaluation of fecal
porphyrins, and measurement of erythrocyte
porphobilinogen deaminase activity is indicated for confirmation or exclusion of the
porphyria and define the type of acute
hepatic porphyrias. The main aim of the treatment is to decrease
aminolevulinic acid,
porphobilinogen, and
porphyrins by reducing hepatic ALAS1 activity. The first measure should always be the avoidance of any porphyrinogenic drugs.
Hemin therapy should not be delayed in the treatment of a severe acute attack.
Gonadotropin-releasing hormone analogs and prophylactic
hemin protocols can be used for selected cases with more than 4 attacks per year.
Givosiran is a promising treatment option for severe cases.