Acute
hepatic porphyrias (AHPs) are a family of four rare
genetic diseases resulting from a deficiency in one of the
enzymes involved in
heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe
abdominal pain, along with other signs and symptoms including
nausea, mental
confusion, hyponatraemia,
hypertension,
tachycardia and
muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as
chronic pain syndrome, neuropathy and
porphyria-associated
kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary
porphobilinogen, [Formula: see text]-aminolaevulinic
acid and
porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and
low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous
hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline
therapy for prevention of attacks and improvement of QoL. Among these, a novel
siRNA-based agent,
givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of
variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.