Work

P032: Systematic literature review of the prevalence and severity of somatic comorbidities in adults with phenylketonuria

Year: 2023

Type: review

Abstract: encephalomyopathy, 23DH2MB was elevated during an admission for altered mental status (AMS) and marked lactic acidosis (20 mmol/L, ref <2.2), but was not seen six months later during an admission for AMS but with a reassuring lactate (2.6 mmol/L, ref <2.2).Conclusion: 2,3-dihydoxy-2-methylbutyric aciduria was first reported with ECHS1 and HIBCH deficiencies, but lacks both sensitivity and specificity as demonstrated in this study.We have identified an additional eight disorders with 23DH2MB, including several with mitochondrial dysfunction.Since the conclusion of this retrospective chart review, 23DH2MB has been identified in other cases, including ACAD9-related mitochondrial complex I deficiency.We hypothesize that the presence of 23DH2MB may be indicative of worsening clinical status and mitochondrial dysfunction as it was transient in several cases.In this study, 2,3-dihydoxy-2-methylbutyric aciduria was identified in approximately 1% of UOA samples, suggesting that it may be more common than previously considered.However, in undiagnosed individuals, its presence should raise suspicion for an underlying metabolic (particularly mitochondrial) disorder and prompt additional evaluation.As 23DH2MB is identified in more individuals and additional genetic diagnoses, further analysis will lend insights into its metabolic origin and determine if it can be used as a surrogate marker of metabolic control in some patients with inherited metabolic disorders.

Source: Genetics in Medicine Open

DOI: 10.1016/j.gimo.2023.100042