Disordered Porphyrin Metabolism: A Potential Biological Marker for Autism Risk Assessment

Abstract

Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger Syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl- (penta) and copro- porphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and copro porphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (p < 0.006) and copro (p < 0.006) concentrations compared to same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic (ROC) curve analysis, we evaluated the sensitivity and specificity of penta, copro and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic.

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

“…Numerous independent studies have found that children with ASDs have significantly elevated levels of urinary porphyrins, which are indicative of greater symptom severity (Geier & Geier, 2006Austin & Shandley, 2008;Geier et al, 2009;Kern et al, 2010Kern et al, , 2011Youn et al, 2010). Although measuring porphyrin levels might not be a valid diagnostic tool for ASDs on its own (Shandley et al, 2014), it may help identify a subgroup of subjects with ASDs (Heyer et al, 2012).…”

Complicity of haem in some adverse drug-reactions

“…50 However, a role for haem in neuronal development and function has been well documented and some reports have linked the risk of a subgroup of autism patients with disturbances of porphyrin metabolism. 51,52 AIP is also associated with an elevated risk of developing hepatocellular cancer. 53 Thus, variants in the haem enzyme genes HMBS, CPOX and PPOX with molecular phenotypic consequences can be considered as genetic predisposing factors for adverse effects of some drugs and hormones in susceptible patients.…”

Current Progress and Challenges in the Search for Autism Biomarkers

“…Heyer et al [113] investigated the urine levels of pentapophyrin and coproporphyrin as potential markers for ASD risk by comparing a group of 30 male children with autistic disorder, 14 with PDD-NOS, and 32 neurotypical controls. ASD children (including PDD-NOS and autism) had higher urinary levels of pentaporphyrin and coproporphyrin compared to age matched controls.…”