Acute Intermittent Porphyria (AIP) is a rare genetic disorder that belongs to a group of diseases known as porphyrias. These conditions are characterized by the abnormal accumulation of porphyrins, essential components in producing heme. Heme is a crucial component of hemoglobin, the protein in red blood cells that carries oxygen. It is the most frequent type of acute porphyria, with a prevalence of 1-2 cases per 15.000 population.
Acute intermittent porphyria genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Acute intermittent porphyria (AIP) is a monogenic disorder with autosomal dominant inheritance marked by the increased formation and excretion of the porphyrins delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG). AIP is caused by a deficiency of the enzyme porphobilinogen deaminase (PBGD), encoded by the HMBS gene, which is involved in the third stage of the heme group synthesis process.
AIP specifically affects the nervous system and can lead to a variety of symptoms during acute attacks. It is caused by mutations in the HMBS gene, which results in a deficiency of the enzyme porphobilinogen deaminase (PBGD), essential for heme synthesis.
Critical features of Acute Intermittent Porphyria include:
- Abdominal Pain: Severe abdominal pain is a hallmark symptom of acute attacks. This pain can be accompanied by nausea, vomiting, and constipation.
- Neurological Symptoms: AIP primarily affects the nervous system, leading to neurological symptoms during acute attacks. These may include muscle weakness, seizures, confusion, hallucinations, and peripheral neuropathy.
- Psychiatric Symptoms: Some individuals with AIP may experience psychiatric symptoms such as anxiety, depression, and psychosis during acute episodes.
- Autonomic Dysfunction: Autonomic nervous system dysfunction can manifest as symptoms like rapid heart rate, high blood pressure, and respiratory distress.
- Hyponatremia: AIP can cause low sodium levels in the blood (hyponatremia), which may contribute to neurological symptoms.
Various factors, including certain medications, alcohol consumption, hormonal changes, and stress, can trigger symptoms of AIP.
Diagnosing AIP involves biochemical testing to detect abnormal levels of porphyrins and their precursors in urine, blood, and stool during an acute attack. Genetic testing can confirm the presence of mutations in the HMBS gene.
Management of AIP focuses on preventing and alleviating symptoms. This may involve avoiding triggers, managing pain, and addressing complications during acute attacks. In severe cases, hospitalization may be necessary.
Patients with AIP may benefit from a comprehensive care plan that includes genetic counseling, lifestyle modifications, and regular monitoring to prevent and manage acute attacks.
About 400 mutations have been described in the HMBS gene. Of these variants, this test analyzes one of the most frequent in patients with AIP, the c.500G>A (p.Arg167Glu) variant that significantly reduces PBGD activity. This variant is more frequent in Argentina and Sweden.
Genetic Testing of Acute Intermittent Porphyria analyzes the four most frequent pathogenic mutations of the HMBS gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
