Short-chain enoyl-CoA hydratase deficiency: a systematic review of clinical spectrum, genotype-phenotype correlations and survival predictors.

ECHS1

Biallelic ECHS1 variants affecting mitochondrial valine catabolism

Short-chain enoyl-CoA hydratase (SCEH) deficiency, caused by biallelic ECHS1 variants, is a rare inborn error of mitochondrial valine catabolism with poorly defined genotype-phenotype correlations. This systematic review (PROSPERO CRD420261376718; PubMed and Scopus; JBI checklists) included 45 studies and 165 patients. Dystonia (67.27%) and developmental delay (60.61%) predominated, globus pallidus involvement was the main imaging finding (62.42%), and urinary 2,3-dihydroxy-2-methylbutyric acid was the most frequent biomarker (41.82%). Neonatal onset was associated with the worst survival (median 28 months) and was the sole independent mortality predictor on multivariate Cox regression (HR 7.41; 95% CI 3.02-18.14; p < 0.001).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The sole independent mortality predictor found is neonatal onset, which reinforces the urgency of molecular diagnosis in metabolic encephalopathy with basal ganglia involvement, but without a new course of action. Despite its title, the review reports no usable genotype-phenotype correlation in its abstract. Individual data drawn from published cases remain exposed to publication bias.

Analysis by Dr Thibaut Benquey