Appropriate Laboratory Evaluation of Porphyrias [Utilization Spotlight]
Since 2012, we have been publishing a Utilization Spotlight in every issue of the Communiqué. Each Spotlight offers a quick view of utilization management best practices in action. This Spotlight is from March 2015.
Evaluating patients for porphyria is complex because of the wide range of nonspecific clinical signs and symptoms. Laboratory testing requires various specimen types for analysis. To facilitate a diagnosis, testing algorithms are available to assist clinicians in identifying the most efficient and effective testing strategies for their patients.
Evaluating patients for porphyria is complex because of the wide range of nonspecific clinical signs and symptoms. Furthermore, laboratory testing requires various specimen types for the analysis of the metabolites, enzymes, and molecular alterations causing disease. To facilitate a diagnosis, testing algorithms are available as inserts in this issue to assist clinicians in identifying the most efficient and effective testing strategies for their patients.
It is important to note, given the complexities of assessing patients for porphyria, errors may occur when ordering individual tests. Experience at Mayo Clinic Biochemical Genetics Laboratory has shown that the majority of requests received for UPGC/Uroporphyrinogen III Co-synthase, which is used to rule out congenital erythropoietic porphyria (CEP), are ordered incorrectly. UPGC is often mistaken for PBGD/Porphobilinogen Deaminase, which is used for the diagnosis of acute intermittent porphyria (AIP). The root cause of many of these orders is likely related to the continued use of older terminology, because porphobilinogen deaminase was previously referred to as uroporphyrinogen I synthase.
Clinically, CEP and AIP have very distinct presentations. CEP is an autosomal recessive condition. It is an extremely rare and severe porphyria which typically has its onset in early infancy. Dermatological signs of CEP include skin photosensitivity, scarring and blistering, red or pink-brown dental discoloration, and hypertrichosis. Growth and cognitive developmental delays are commonly observed in individuals with CEP. Conversely, AIP is an autosomal dominant condition and one of the most common types of porphyria. Patients usually present during puberty or later and may experience potentially life-threatening acute episodes of neuropathic symptoms including severe abdominal pain, peripheral neuropathy, and psychiatric features. Medications, alcohol, infection, starvation, and hormonal changes may precipitate acute episodes.
When the UPGC test is ordered, the current laboratory process involves contacting the ordering physician via fax or telephone to evaluate the order for accuracy and to verify the appropriateness of testing the patient for CEP versus AIP. This provides the physician an opportunity to cancel an unnecessary test and have the clinically appropriate assay performed. If a reply is not received within one week, the UPGC is canceled and the specimen held for one month. If testing was canceled and the diagnosis of either AIP or CEP is warranted, the clinician may contact the Biochemical Genetics Laboratory consultant or genetic counselor on call (1-800-533-1710) within one month to obtain approval for testing. To ensure appropriate utilization of services and management of health care expenses, this verification process is completed each time the UPGC test is ordered.