Although in some cases the neurodevelopmental impairment is thought to be the consequence of toxic substrate accumulation, such as in ADSL deficiency and 5‐amino‐4‐imidazolecarboxamide‐ribosiduria because of ATIC deficiency,93 other conditions including Arts syndrome (phosphoribosylpyrophosphate synthase deficiency) and severe combined immunodeficiency because of adenosine deaminase deficiency show evidence of more subtle alterations of CNS developmental processes.92, 94. This evidence concerns the gene ADSL and hyperinsulinemic hypoglycemia, familial, 4.