LCGreen I–Based Real-Time PCR Assays for Detecting Common ASL and HMGCL Variants

Abstract

Argininosuccinic aciduria (ASAuria; OMIM 207900) is an autosomal recessive inborn error of the urea cycle caused by deficiency of the enzyme argininosuccinate lyase (ASL; EC 4.3.2.1) (1). A novel nonsense variant, ASL :p.Q354STOP, is the most common variant underlying ASAuria in the Saudi population and accounts for ∼50% of all cases (2). Currently, diagnosis for ASAuria is based on electrospray tandem mass spectrometry (ESI-MS/MS) of dried blood spots (DBS) (3); however, although it is rapid and specific, this method is not suitable for prenatal diagnosis and carrier detection. Another autosomal recessive inborn error of metabolism is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) lyase deficiency (HMGCLD; OMIM 246450). HMG-CoA plays a key role in ketone body formation. Biochemical diagnosis of HMGCLD is made by MS/MS using DBS and is confirmed by organic acid analysis (4). HMGCLD is relatively common in the Saudi population (5), in which a novel variant, c.122G>A, leading to substitution of glutamine for arginine at position 41 ( HMGCL :p.R41Q), has been described (6). We …