Acute Intermittent Porphyria



What is Acute Intermittent Porphyria?

Porphyria is a group of diseases that entails defects in metabolism of heme resulting in too much secretion of porphyrin precursors and pophyrins. Acute intermittent porphyria (AIP), is one of those porphyrias. This hereditary type of porphyria is autosomal dominant. Acute intermittent porphyria is usually caused by decreased levels of porphobilinogen deaminase (PGBD), also called as hydroxymethylbilane synthase. Generally, the low levels of PGBD is insufficient to cause symptoms, but other factors that can activate it such as drugs, dietary changes, and drugs trigger the symptoms. It usually manifest in neuropathies, constipation and mostly, abdominal pain. Usually, patients does not develop symptoms, but the most common is abdominal pain. However, Acute intermittent porphyria patients do not develop symptoms like a rash unlike the majority types of porphyria.

Causes

Acute intermittent porphyria is a product of mutation in the enzyme gene of hydroxymethylbilane-synthase (HMB-synthase), that is also called  uroporphyrinogen I synthase or porphobilinogen deaminase.

Trigger Factors

There are also other triggering factors that are present, such as

  1. hormones,
  2. dietary changes, and
  3. drugs.

Activating factors can sometimes be unidentified.

Acute attacks are often a result of provocation by means of drugs such as

  1. sulfonamide antibiotics
  2. barbiturates
  3. anti-seizure drugs
  4. metoclopramide
  5. rifampin and
  6. alcohol

Attacks may occur during later part of menstrual cycle or after ovulation in women. In an effort to lose weight, reduction of food intake, surgery, infections, and stressful situations may also trigger an attack.

Symptoms

People who inherited Acute intermittent porphyria gene; a mutation in PBGD, does not develop symptoms. Hence, the disease with a symptom could skip generations or is only documented in a single person in a family. The nonspecific symptoms account for the delay in diagnosis and there is high variability in its presentation.

Symptoms attack acutely, often in thirties or forties in a person’s life and are commonly seen in women more than in men. Acute intermittent porphyria attacks develop in hours or days and continue up to days or even weeks and it depends upon the precipitating factors as well as treatment. Skin manifestations are not present. However, there are rare exceptions that Acute intermittent porphyria patients with advanced renal failure develops plasma porphyrins elevation and blistering lesions.

Severe abdominal pain

In Acute intermittent porphyria, severe abdominal pain is the most common symptom. It is usually steady, severe, and poorly localized. However, it is occasionally cramping and it frequently is accompanied by constipation and other signs of ileus; abdominal distention, vomiting, nausea, and decrease in bowel sounds.

Other symptoms in Acute intermittent porphyria

  1. Pain in arms and legs as well as in the back
  2. Muscle weakness caused by damage in the nerves that supplies the muscles
  3. Urinary retention
  4. Confusion, seizures and hallucinations
  5. Palpitation

acute intermittent porphyria pictures

Diagnosis

This disease is unusual and can copy symptoms of other common conditions, it usually is not suspected. On a side note, a false positive also happens. Misdiagnosis is common when there is an incorrect theory of having a porphyria.  A finding of Porphobilinogen (PBG) and Delta-aminolevulinic acid (ALA) levels that are increased in urine institutes that any of the acute porphyrias is present. The diagnosis of Acute intermittent porphyria is present if there is a deficiency in PBGD levels in a normal red blood cell. However, it is not a reliable marker of Acute intermittent porphyria because not all Acute intermittent porphyria patients illicit a deficient PBGD in their red blood cells.

If a known relative or direct family has been diagnosed with Acute intermittent porphyria, the enzyme PBGD is relatively low in the red blood cells. There are also cases in which low levels of the enzyme PBGD in red blood cells is transferred genetically to their offspring. Identified latent cases are advised to avoid  the cause and take specific precautions to prevent acute attacks. However, some families with AIP, has a deficient PBGD level in their liver and some tissues and is normal in red blood cells. False low values sometimes happen because of problems in collection and transport of the sample.

DNA, the cellular material that records all the information of the genes of an individual. A lot of mutations had been identified in the part of the DNA which entails the gene for PBGD. Almost every Acute intermittent porphyria family has a different kind of mutation in their gene. Within that family, there is an individual who inherits a same mutation of low levels of PBGD. It is in an advantage to know the exact kind of mutation in a certain family because that knowledge is the basis for identification of the gene carriers of AIP in a DNA test. This is a much precise method than measurement of PBGD enzyme activity in a red blood cell. During the present time, Acute intermittent porphyria and other porphyria testing through DNA tests is only available in some research laboratories.


Treatment

Hospitalization is needed for the acute attacks of Acute intermittent porphyria. Generally, close observation is required and medications for vomiting and nausea, and pain is given.

Diet Modification

To suppress the activity of the disease, high intake of carbohydrates or glucose are given and it can either be given intravenously or per orem.

Heme therapy

Heme therapy given intravenously is more effective in suppressing activity of the disease. It is much better if heme is started in an early stage of the attack and the response of the AIP patient is better. Thus, waiting for the effectivity of the glucose  therapy and delaying giving heme treatment is not advisable unless it is a mild attack.

Water & Salt balance

During an attack treatment, water and salt balance must be monitored and other potentially harmful drugs must be stopped. These medications are sulfonamides, barbiturates and many more. Attacks are often caused by low carbohydrate and calorie intake in an attempt to lessen weight meaning dietary measures are very important. Attacks of pre-menstruation resolves quickly by manipulating hormones.

Acute intermittent porphyria is dangerous if there is no confirmation of the diagnosis and the patient is given harmful drugs. Prognosis is usually better if diagnosis is done in early stages and treatment as well as preventive measures are started before there is some presence of nerve damage. Some people develop chronic pain even if the usual thing is that symptoms resolve when Acute intermittent porphyria attack happens. After a severe attack, progress in muscle weakness and nerve damage improves after several months or longer. Mental changes can also occur, but are not chronic.

A medic alert bracelet is also important as the disease is lifelong. However, it is advisable for Acute intermittent porphyria patients who had some attacks, but are not as important in latent cases. Other diseases can also develop and it may not always be related to porphyria.

Diet

Diet in Acute intermittent porphyria patients include intake of normal or high carbohydrates. As such, intake of carbohydrates must not be restricted even for a short period of time.

If AIP patient desires weight loss, it is advisable to consult to a  doctor and to a dietician to round up the normal caloric intake for the certain patient. It is appropriate to prescribe a diet 10% below normal caloric levels for the patient. Gradual weight loss will be attained and pophyria attacks are still prevented.



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