Acute Intermittent Porphyria
Related Gene(s): HMBS
Acute intermittent porphyria (AIP) is a deficiency of the enzyme hydroxymethylbilane synthase (also known as porphobilinogen deaminase) in the heme biosynthesis pathway, due to a mutation in the HMBS gene. The disorder is inherited in an autosomal dominant manner. The enzyme deficiency alone is not sufficient to produce the symptoms of AIP, and other activating factors, such as drugs, hormones, and dietary changes, must be present. Occasionally, activating factors cannot be identified.
Most people who have a mutation in the gene for AIP never develop symptoms. This is referred to as “latent” AIP. Symptoms usually develop after puberty in men and women. Acute attacks are typically characterized by severe abdominal pain. However, sometimes the pain may begin in the chest, back, or thighs. Patients also experience nausea, vomiting, constipation, and increased heart rate and blood pressure. These symptoms and signs are all due to the effects of the disease on the nervous system. Confusion, convulsions, and muscular weakness, due to neurologic impairment, may lead to paralysis. An acute attack usually lasts for days. Recovery from severe paralysis is generally slow.
Full DNA analysis of the HMBS gene is performed by full gene sequencing of all exons (coding regions), 20-30 base pairs into the introns (including splice sites), and the promoter region. This methodology should identify >98% of mutations reported in the Human Gene Mutation Database, as well as novel mutations. Targeted mutation analysis can be performed for family members of individuals whose HMBS gene mutation has been identified previously.
Prenatal diagnosis is also available. Prior to ordering prenatal testing, please contact our laboratory at 212-241-7518 to discuss.
- Testing requires prior documentation of parental mutations.
- Chorionic villi: 5-10 mg in conical tube with sterile saline or transport media
- Amniotic fluid: 10 mL in conical tube
- Cultured cells: Two confluent T-25 flasks
- Additionally, please send:
- Maternal blood: 5-10 mL in EDTA tube (lavender top) required to perform MCC studies on all prenatal samples and in case maternal confirmation studies are necessary
- Paternal blood: 5-10 mL in EDTA tube (lavender top) in case paternal confirmation studies are necessary
- For adults
- Full DNA sequence analysis: 10-20 mL of whole blood in EDTA (anticoagulant) tubes (lavender top) or extracted DNA (50 µL with concentration of 200 ng/µL)
- Targeting mutation analysis: 10-20 mL of whole blood in EDTA (anticoagulant) tubes (lavender top) or extracted DNA (30 µL with concentration of 200 ng/µL) or buccal cells (buccal brushes must be requested from laboratory)
- For newborns or children
- Blood: 2 mL in pediatric EDTA tube (lavender top) or 2 mL in pediatric ACD tube (yellow top) from patient
- Ship at room temperature
- Prenatal: 3-5 days
- Postnatal: 10-14 days