Laboratory Diagnosis of Porphyria

Abstract

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

Microcytosis in Erythropoietic Protoporphyria

“…Twenty Italian unrelated EPP patients and 20 sex and aged-matched healthy volunteer individuals were included in the study before starting oral iron supplementation if necessary. The EPP patients, 11 males (34 ± 10 years) and nine not pregnant females (37 ± 10 years), all exhibited a typical plasma fluorescence peak at 632–635 nm and an increase of total erythrocyte protoporphyrin (ePP) concentrations with predominance of free protoporphyrin (PPIX; Di Pierro et al, 2021 ). In addition, all patients had a classical EPP genetic diagnosis with a loss-of-function FECH mutation in trans to the hypomorphic allele.…”

Case Report: Variegate porphyria disclosed by post-gastric bypass complications and causing predominant painful sensorimotor axonal peripheral neuropathy

“…A few weeks after undergoing a gastric bypass procedure with several postoperative complications, this middle-aged patient developed an abrupt proximal-predominant areflexia and flaccid tetraparesis associated with sensory symptoms (including neuropathic pain) involving the four limbs. After a thorough and stepwise workup excluding etiologies, her neurological symptoms were most likely caused by VP, based on typical abnormalities of urinary and fecal biomarkers ( Di Pierro et al, 2021 ) and the finding of a new heterozygous mutation in the PPOX gene of pathological potential never reported before. Indeed, being a deletion, the observed mutation caused a frameshift and a truncated transcript most likely leading to the synthesis of a dysfunctional enzyme and subsequent toxic porphyrin precursors ( Barbaro et al, 2013 ).…”

Two Novel Hydroxymethylbilane Synthase Splicing Mutations Predispose to Acute Intermittent Porphyria

“…This study was approved by the local ethics committee (Ethics Committee of Shanxi University, Ethics number: SXULL2021063, 10 June 2021) and written informed consent was obtained from all participating patients. Both families are from mainland China, and the probands were diagnosed by doctors because of their elevated ALA or PBG levels or clinical symptoms consistent with acute hepatic porphyria [30].…”