Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene

Abstract

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11;

Genetic diagnosis of basal ganglia disease in childhood

“…We found 36 variants: 25 were reported as pathogenic or likely pathogenic, and 11 were novel (pathogenic n =5, likely pathogenic n =5, variant of unknown significance n =1). In six out of 11 novel variants, functional studies and biomarker analysis had previously demonstrated their contribution to the phenotype 5,10–14 …”

“…Methylmalonic aciduria was observed in a patient with SUCLG‐ related Leigh syndrome. Patients with HIBCH defects showed high levels of 3‐hydroxyisobutyryl carnitine or 3‐hydroxyisovaleric acid 10 (Table S1).…”

“…Nine patients from this study were previously reported by our group. 5,[9][10][11][12][13][14] SPSS version 24 (IBM Corp., Armonk, NY, USA) and RStudio (RStudio, Inc., Boston, MA, USA) were used for statistical analyses.…”

“…In six out of 11 novel variants, functional studies and biomarker analysis had previously demonstrated their contribution to the phenotype. 5,[10][11][12][13][14] In eight patients with negative genetic studies, reassessment of clinical charts and neurological evaluation identified previously acquired events that could be associated with the clinical and radiological phenotype (Fig. 1a and Fig.…”

A Novel Variant of the Short-Chain Enoyl-CoA Hydratase-1 Gene Presenting with a Mild Phenotype: The Second Case Report from India

“…2 The phenotypic spectrum of the disease range from neonatal-onset severe phenotype with myriad of neurological and multisystem manifestations 7 to milder phenotypes presenting at >2 years with paroxysmal and exercise induced dyskinesias triggered by increased energy demand. 8,9 However, multiple types of persistent hyperkinetic movement disorders 10 have not yet been described. Phenotypic heterogeneity exists for the same genotype, often making the diagnosis challenging.…”