Compared to individuals with single homotetrameric or multiple homo and heterotetrameric proteins, those predicted not to synthesize any functional enzyme protein had significantly lower expression of <i>ALDH5A1</i> (<i>p</i> = 0.001), worse overall clinical outcomes (<i>p</i> = 0.008) and specifically more severe cognitive deficits (<i>p</i> = 0.01), epilepsy (<i>p</i> = 0.04) and psychiatric morbidity (<i>p</i> = 0.04). Here, ALDH5A1 is linked to Cognitive impairment.