Molecular analysis using targeted next generation DNA sequencing and clinical spectrum of Mexican patients with isovaleric acidemia

In this study, clinical summaries, biochemical measurements and targeted next generation sequencing (tNGS) data from the IVD gene were compared in 13 Mexican patients. The main symptoms were vomiting, feeding refusal, abdominal pain, impaired alertness, lethargy, stupor, coma; hypotonia, ataxia, hallucinations, seizures; anemia, neutropenia and pancytopenia. Mean blood concentration of isovalerylcarnintine was above the reference value (0.5 µM) in symptomatic patients, as well as in the screen positive newborns with 8.78 µM and 2.23 µM respectively. The molecular spectrum of this cohort was heterogeneous, with 14 different variants identified, seven were previously-described, and seven were novel. The most frequent variant was c.158G>C (p.R53P). In this study, we found a long diagnostic delay (average of 44 months) thus, it is essential to increase physicians’ awareness of this treatable condition. Biochemical IVA NBS accompanied by molecular studies such as tNGS will permit identification of potentially asymptomatic forms of the disease, allowing better genotype-phenotype relationship, management decisions and follow-up.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research