What is the diagnosis and treatment for Propharia?

Diagnosis and Treatment of Porphyria

The diagnosis of porphyria requires biochemical confirmation with specific tests before proceeding to genetic testing, as genetic testing alone can lead to false diagnoses and potentially harmful treatment decisions. 1

Types of Porphyria

Porphyrias are a group of rare inborn errors of metabolism caused by abnormal functioning of haem biosynthesis enzymes and are associated with various clinical presentations:

• Acute neurovisceral porphyrias: Characterized by severe abdominal pain and neuropsychiatric symptoms that may require specialized intensive care 2
• Cutaneous porphyrias: Present with bullae on sun-exposed areas or acute painful photosensitivity 2
• Erythropoietic porphyrias: May present in newborns (congenital erythropoietic porphyria) or children (erythropoietic protoporphyria) 2

Diagnostic Approach

Initial Evaluation

• For suspected acute neurovisceral porphyria, collect a random urine sample for quantitative measurement of porphobilinogen (PBG) and δ-aminolevulinic acid (ALA), and protect all samples from light by covering collection tubes with aluminum foil 1
• Use morning or spot urine samples normalized to creatinine excretion (avoid 24-hour collections) for suspected acute neurovisceral porphyria 1
• Normal PBG/ALA levels during symptoms effectively rule out acute porphyria 1
• Significantly elevated PBG (>10× upper limit of normal) confirms acute porphyria attack 2

Biochemical Testing

• Diagnosis requires demonstration of increased accumulation and excretion of porphyrins and porphyrin precursors in urine, feces, and blood 2
• Different porphyrias cause accumulation of the same metabolites, so most markers cannot be interpreted individually 2
• For acute porphyrias, during an attack, the PBG/creatinine ratio is typically increased to more than 10 times the upper limit of normal 2

Genetic Testing

• Genetic testing should only be performed after biochemical confirmation of porphyria 1
• For acute porphyrias, sequence and analyze gene dosage of HMBS (for AIP), PPOX (for VP), CPOX (for HCP), or ALAD (for ALAD deficiency) 2
• For cutaneous porphyrias like PCT (most common type), only 20% have pathogenic UROD gene variants (familial PCT) 2
• For EPP, analyze FECH gene and intronic variant c.315-48T>C 1

Treatment Approaches

Acute Porphyria Attacks

• Identify and avoid or eliminate factors that precipitate or worsen acute attacks 2
• Avoid medications that can trigger attacks by consulting publicly available drug databases (http://www.porphyriafoundation.com/drug-database, http://www.drugs-porphyria.org/) 2
• For patients undergoing surgical procedures, plan anesthesia using agents that are safe in acute hepatic porphyrias (AHPs) 2
• Consider prophylactic hemin infusion prior to surgery for patients with frequently recurring attacks 2

Management of Chronic Complications

• Monitor and treat chronic hypertension to prevent renal damage 2
• Obtain liver function tests for all patients at baseline; evaluate patients with persistently abnormal serum aminotransferases for other causes of liver disease 2
• Consider neurological consultation between attacks for better assessment of positive neurological findings or unexplained symptoms 2
• Nerve conduction and electromyographic studies may detect chronic neuropathy as the cause of ongoing pain, sensory loss, or muscle weakness 2

Lifestyle Recommendations

• Maintain a balanced diet and avoid prolonged fasting or crash dieting 2
• Avoid alcohol and smoking, particularly for patients with severe recurrent symptoms 2
• For patients with HCP and VP who have cutaneous lesions, avoid sunlight exposure and wear protective clothing 2
• Medical alert bracelets are recommended for all AHP patients 2

Family Screening and Genetic Counseling

• All heterozygotes (whether symptomatic or not) should receive appropriate genetic counseling about inheritance 2
• For acute porphyrias, healthy at-risk family members are advised to have genetic testing so those with pathogenic variants can avoid precipitating factors 2
• Studies in AIP families have shown that the likelihood of an acute attack is much higher in family members (estimated at 12.7% excluding the proband) 2

Common Pitfalls to Avoid

• Performing genetic testing without prior biochemical confirmation can lead to false diagnoses 1
• Relying on urinary total porphyrins alone for diagnosing acute porphyria is misleading 1
• Failing to protect samples from light exposure can cause falsely low results 1
• Analyzing irrelevant tests for the clinical situation (e.g., urinary total porphyrins for a patient with acute painful photosensitivity symptoms) 2
• Using qualitative screening tests without following up with quantitative and more sensitive assays 2