Disease you might heard, but stories might not : Porphyria

You might have heard about this rare disease, known as Acute Intermittent Porphyria (AIP). In this rare disorder patients experience symptoms such as:

• Pain in the abdomen (most common, 95% of patients experience)
• Psychological symptoms (Anxiety, agitation, hallucination, hysteria, delirium, depression
• Peripheral neuropathy (Patchy numbness and paresthesia)
• Pee abnormality (Dysuria, urinary retention/incontinence of dark urine)
• Precipitated by Drugs (e.g., Barbiturates, oral contraceptives, Sulfa drugs)

AIP is a rare autosomal dominant metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of  Hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase.

Traces from History

We find the traces back to the history regarding this rare disorder, Son of Frederick and Augusta of Saxe-Coburg-Gotha, King George III had symptoms of intractable insomnia, confusion, he was seen talking to trees and hallucinations, severe abdominal pain, constipation, lameness muscular weakness, racing pulse, painful blisters and skin lesions, sensitivity to light, convulsions and dark urine.

His case has been closely researched and the diagnosis of Variegate Porphyria was

made. 

Cases Studies: Acute porphyrias

At times it takes a long time to diagnose Acute porphyrias, and here are some instances:

Case 1:

• A 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. 
• The patient presented with abdominal pain, nausea, and vomiting during her first pregnancy. Diagnosed as hyperemesis gravidarum, and was treated with intravenous (IV) fluids and antiemetics. The patient improved and delivered a healthy child.
• After 2 months, the patient presented with a bout of severe abdominal pain (diagnosed as cholecystitis), followed by repeated seizures, hyponatraemia, elevated and uncontrolled blood pressure, sinus tachycardia, delirium, lower limb weakness, hyporeflexia, and psychological abnormalities.
• Later DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene confirming the diagnosis of acute intermittent porphyria (AIP).

Case 2:

• An 8-year-old boy with a history of global developmental delay and intractable seizures.
• He presented with a 1-month history of increasing lethargy, persistent seizures, poor oral intake, and dark-colored urine. He was on four different antiepileptic medications. 4 months before the current admission, his seizures increased and he started on clobazam, which resulted in some improvement. His patients reported that he appeared to have generalized myalgia.
• Later in a Porphyria-specific test it was diagnosed with Sequencing the HMBS gene was positive for a missense mutation, R321H confirming the diagnosis of acute intermittent porphyria (AIP).

Case 3:

• A 21-year-old female with recurrent abdominal pain that was attributed to endometriosis.
• She was treated with depot medroxyprogesterone acetate with no improvement and required admission to the hospital for pain control with intravenous (IV) morphine. 
• After 5 days of pain and anorexia, she had a generalized seizure.
• Later in a Porphyria-specific test, it was diagnosed that significantly elevated urine porphobilinogens and normal urinary coproporphyrins suggested acute intermittent porphyria (AIP).

Case 4:

• 26-year-old female, hospitalized in the intensive care unit (ICU) for acute respiratory failure associated with acute polyradiculoneuropathy considered initially as Guillain-Barré syndrome (GBS). 
• Her condition began with acute abdominal pain which mimicked appendicitis and an appendectomy was performed.
• Worsening neuropathy led to respiratory failure requiring mechanical ventilation and she was transferred to an ICU.
• Clinical findings on admission included proximal weakness with hypoesthesia, facial diplegia, and abolished tendon reflexes.
• Central nervous system (CNS) signs included blurring, hallucinations, and seizures.
• Hypertension, sphincter dysfunction, and severe gastroparesis impeding enteral feeding were initially ascribed to dysautonomia.
• The diagnosis of acute intermittent porphyria (AIP) was finally confirmed once porphyria-specific tests were undertaken but with significant delay.

Conclusion:

• Undiagnosed patients are often followed in intensive care units for weeks, because of unconsciousness, severe paresis and hypoventilation. Those, who are undiagnosed or are diagnosed at the late stage, have markedly increased mortality during an acute attack.
• A delayed diagnosis and/or an inappropriate treatment of an acute porphyric attack may have a fatal outcome.
• Based on current guidelines, Human hemin therapy (Normosang) is the first-line treatment and treatment of choice for Acute attacks of Acute Hepatic Porphyria.

Reference: Recordati Rare Diseases (https://www.recordati.com/en/)