Acute intermittent porphyria

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Acute intermittent porphyria ( AIP ) is a genetic metabolic disorder affecting heme production, a prosthetic group that binds oxygen from hemoglobin. This is characterized by a deficiency of the porphobilinogen deaminase enzyme. Inheritance is more dominantly autosomal; However, an autosomal recessive form of this disorder has occurred. The incidence is estimated to be between 5 and 10 in 100,000.

Video Acute intermittent porphyria

Signs and symptoms

The signs and symptoms of AIP may vary. Severe and less localized abdominal pain is a very common symptom (found in 95% of those affected by AIP). Urinary signs and symptoms such as painful urination, urinary retention, urinary incontinence, or dark urine have also been known to occur. The signs of psychiatry and the symptoms of AIP can manifest as anxiety, paranoia, irritability, delusions, hallucinations, confusion, and depression. Signs indicating increased activity of the sympathetic nervous system may be evident including tachycardia, hypertension, palpitations, orthostatic hypotension, sweating, anxiety, and tremors. Other neurological signs and symptoms of AIP include seizures, peripheral neuropathy, abnormal sensations, chest pain, foot pain, back pain or headache, and coma. Nausea, vomiting, constipation, and diarrhea may also occur. Proximal muscle weakness usually begins in the arm is a characteristic; there may be muscle pain, tingling, numbness, weakness or paralysis; Muscle weakness seen in AIP can develop to include respiratory muscles that cause respiratory failure and can be fatal.

AIP patients have an increased risk of developing hepatocellular carcinoma, melanoma, lymphoma, chronic hypertension, chronic kidney disease, and chronic pain.

Maps Acute intermittent porphyria

Pathophysiology

AIP is caused by mutations in the HMBS gene, which encodes a porphobilinogen deaminase enzyme.

A Swedish study showed that about 90% of cases of acute intermittent porphyria are due to mutations in the HMBS gene that cause a decrease in the amount of enzymes, and to a lesser extent by mutations that lead to decreased activity of each enzyme molecule. Under normal circumstances, heme synthesis begins in the mitochondria, into the cytoplasm, and ends back in the mitochondria. However, without porphobilinogen deaminase, the necessary cytoplasmic enzymes, heme synthesis can not be completed, and porphobilinogen metabolites accumulate in the cytoplasm.

Both endogenous and exogenous factors can cause acute attacks, such as certain drugs, alcohol, infections, low calorie intake, or changes in sex hormone balance during the menstrual cycle or pregnancy. These factors induce heme synthesis either directly or indirectly through activation of ALA synthase in the liver, thereby increasing the accumulation of the substrate into the deficient enzyme.

Patients with AIP are often misdiagnosed with psychiatric illness. Subsequent treatment with anti-psychotic increases porphobilinogen accumulation, thereby aggravating the disease sufficiently so it can be fatal. Mutation of genes lies on chromosome 11q23.3. Mutations include deletion, inversion, and translation.

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Diagnosis

Urine and serum show elevated porphobilinogen levels.

Red blood cell test for porphobilinogen deaminase level.

Test

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Treatment

If drugs have caused an attack, stop giving offensive substances is very important. It is recommended to give high infusion of carbohydrate (10% glucose), which can help recovery.

Haematin and heme arginate are the treatment of choice during an acute attack. Heme is not a curative treatment, but it can shorten attacks and reduce the intensity of attacks. Side effects are rare but can be serious. Pain is very severe and almost always requires the use of opiates to reduce it to a tolerable level. Pain should be treated as early as possible medically because of its severity.

Nausea can be severe; it may respond to phenothiazine drugs but is sometimes stubborn. Hot or bath baths can reduce temporary nausea, but may pose a burn or fall risk.

Seizures often accompany this disease. Most seizure medications worsen this condition. Treatment can cause problems: Barbiturates and Primidone should be avoided because they usually trigger symptoms. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer the possibility of a regimen for seizure control.

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Famous sufferers

One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his brothers, especially his brother Theo, suffer from AIP and syphilis. Another theorized opinion is King George III of the United Kingdom who even has a medal to commemorate his "curing". His great-grandmother Prince William of Gloucester was reliably diagnosed with porphyria variegate in 1968. Perhaps the philosopher Jean-Jacques Rousseau suffered from porphyria.

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References

Source of the article : Wikipedia