HMBS Gene, Full Gene Analysis
Confirming a diagnosis of hydroxymethylbilane synthase deficiency/acute intermittent porphyria
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hydroxymethylbilane synthase (HMBS) deficiency is an autosomal dominant disorder with incomplete penetrance that can present as acute intermittent porphyria (AIP). The most common clinical presentation of AIP is abdominal pain. Acute attacks can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. Respiratory paralysis can progress to coma and death. HMBS deficiency can also be without clinical or biochemical manifestations.
Acute attacks may be prevented by avoiding both endogenous and exogenous triggers. These triggers include porphyrogenic drugs, hormonal contraceptives, fasting, alcohol, tobacco and cannabis.
The measurement of porphobilinogen deaminase (PBG-D) enzyme activity in erythrocytes facilitates detection of AIP during latent periods, and also confirms a biochemical diagnosis during acute episodes. However, a normal result does not completely exclude a diagnosis of HMBS deficiency/AIP. The preferred diagnostic test is molecular genetic testing of the HMBS gene.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A small percentage of individuals who have a diagnosis of acute intermittent porphyria (AIP) may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic alterations). The absence of a mutation(s), therefore, does not eliminate the possibility of the diagnosis of AIP. For testing asymptomatic individuals it is important to first document the presence of an HMBS gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 1-800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Mutations in other genes, such as CPOX and PPOX have been shown to cause other forms porphyrias. Abnormalities in these genes are not detected by this assay.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Thunell S: Hydroxymethylbilane Synthase Deficiency. In GeneReviews (Internet). Edited by RA Pagon, TD Bird, CR Dolan, K Stephens. University of Washington, Seattle WA; 1993-2005 Sep27 (updated 2011 Sep 01)
2. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutierrez P, Frank J: The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 2010 Oct;24(5):593-605
3. Anderson KE, Bloomer JR, Bonkovsky HL et al: Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005 Mar 15;142(6):439-450