Biochemical Diagnosis of Acute Hepatic Porphyria: Updated Expert Recommendations for Primary Care Physicians.

Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term complications. Diagnostic biochemical testing is widely available and effective, but a substantial time from symptom onset to diagnosis often delays treatment and increases morbidity. A panel of laboratory scientists and clinical AHP specialists collaborated to produce recommendations on how to enhance biochemical diagnosis of AHP in the USA. AHP should be considered in the differential diagnosis of unexplained abdominal pain, the most common symptom, soon after excluding common causes. Measurement of porphobilinogen (PBG) and porphyrins in a random urine sample, with results normalized to creatinine, is recommended as an effective and cost-efficient initial test for AHP. Delta-aminolevulinic acid testing may be included but is not essential. The optimal time to collect a urine sample is during an attack. Substantial PBG elevation confirms an AHP diagnosis and allows for prompt treatment initiation. Additional testing can determine AHP subtype and identify at-risk family members. Increased awareness of AHP and correct diagnostic methods will reduce diagnostic delay and improve patient outcomes.

Improving accuracy of Tay Sachs carrier screening of the non-Jewish population: analysis of 34 carriers and six late-onset patients with HEXA enzyme and DNA sequence analysis.

The purpose of this study was to determine whether combining different testing modalities namely beta-hexosaminidase A (HEXA) enzyme analysis, HEXA DNA common mutation assay, and HEXA gene sequencing could improve the sensitivity for carrier detection in non-Ashkenazi (AJ) individuals. We performed a HEXA gene sequencing assay, a HEXA DNA common mutation assay, and a HEXA enzyme assay on 34 self-reported Tay-Sachs disease (TSD) carriers, six late-onset patients with TSD, and one pseudodeficiency allele carrier. Sensitivity of TSD carrier detection was 91% for gene sequencing compared with 91% for the enzyme assay and 52% for the DNA mutation assay. Gene sequencing combined with enzyme testing had the highest sensitivity (100%) for carrier detection. Gene sequencing detected four novel mutations, three of which are predicted to be disease causing [118.delT, 965A-->T (D322V), and 775A-->G (T259A)]. Gene sequencing is useful in identifying rare mutations in patients with TSD and their families, in evaluating spouses of known carriers for TSD who have indeterminate enzyme analysis and negative for common mutation analysis, and in resolving ambiguous enzyme testing results.