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Acute hepatic porphyria (AHP)
Hepatic porphyrias are genetic disorders caused by the defect in an enzyme involved in heme synthesis and accumulation of heme precursors
Prevalence
5 - 10 / 100 000
5 / 100,000
US Estimated
1 - 9 / 100,000
Europe Estimated
Age of Onset
Adult
ICD-10
E80.21
E80.29
Inheritance Pattern
Autosomal dominant
Autosomal recessive
Mitochondrial/Multigenic
X-linked dominant
X-linked recessive
5 Facts you should know
FACT
Neurological attacks including seizures, psychosis, severe abdominal/back pain, and acute polyneuropathy – are a hallmark of AHP
FACT
The most common presenting symptom is neuropathic abdominal discomfort
FACT
Cutaneous manifestations such as photosensitive blistering rash or hypertrichosis are also common
FACT
All racial and ethnic groups are affected by acute hepatic porphyrias but the symptomatic attacks occur most commonly in females between 14 and 45 years of age
FACT
The diagnosis of AHP is often missed or delayed because the clinical symptoms mimic other more common disorders
Common signs & symptoms
Symptoms typically evolve over hours to days and may recur.
Abdominal
• Severe, diffuse abdominal pain (often disproportionate to exam findings)
• Nausea, vomiting, constipation (more common than diarrhea)
• Abdominal distension, ileus
Neurologic
• Peripheral motor neuropathy (proximal > distal; may progress to paresis or paralysis)
• Sensory neuropathy (paresthesias)
• Autonomic neuropathy:
• Tachycardia
• Hypertension
• Diaphoresis
• Cranial nerve involvement (less common)
• Seizures (often precipitated by hyponatremia or porphyrinogenic drugs)
Psychiatric
• Anxiety, agitation
• Insomnia
• Depression
• Psychosis or confusion during severe attacks
Electrolyte and systemic
• Hyponatremia (commonly SIADH-related)
• Dark or reddish urine (due to oxidized porphyrins; may darken on standing)
• Fatigue between attacks in recurrent disease
Cutaneous (subset only)
• In variegate porphyria (VP) and hereditary coproporphyria (HCP):
• Photosensitivity
• Fragile skin, blistering, erosions
Triggers
• Porphyrinogenic medications
• Fasting or caloric restriction
• Hormonal fluctuations (e.g., luteal phase)
• Infections, stress
• Alcohol
• Smoking
Current treatments
Acute attack management
• Intravenous hemin (cornerstone of treatment)
• Suppresses hepatic ALA synthase and halts neurotoxic precursor production
• Carbohydrate supplementation (oral or IV glucose) in mild attacks or as adjunct
• Symptomatic management
• Opioids for pain control
• Antiemetics for nausea/vomiting
• Careful correction of hyponatremia and other electrolyte abnormalities
• Immediate discontinuation of precipitating factors
• Porphyrinogenic medications, fasting, alcohol, hormonal triggers
Prevention of recurrent attacks
• Givosiran (RNA interference therapy)
• Indicated for adults with recurrent AHP attacks
• Reduces hepatic ALAS1 expression and attack frequency
• Avoidance of triggers
• Medication review, infection management, nutritional stability
• Hormonal modulation (selected cases)
• For cyclic attacks related to the menstrual cycle (specialist guided)
Long-term management
• Multidisciplinary follow-up (hepatology, neurology, pain management)
• Monitoring for chronic complications
• Chronic pain, neuropathy
• Chronic kidney disease
• Hepatocellular carcinoma (long-term risk in AHP)
Clinical note: Liver transplantation is rarely considered and reserved for exceptional, refractory cases with severe disease burden.
References:
Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood. 2012;120(23):4496–4504. Puy H, Gouya L, Deybach JC. Porphyrias. Lancet. 2010;375(9718):924–937. Anderson KE, Sassa S, Bishop DF, Desnick RJ. Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. Hematology Am Soc Hematol Educ Program. 2005:14–27. Balwani M, Sardh E, Ventura P, et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N Engl J Med. 2020;382:2289–2301. National Organization for Rare Disorders (NORD). Acute Hepatic Porphyrias. American Porphyria Foundation. Acute Hepatic Porphyria – Clinical Overview.