1 - Metabolic Unit, Pediatric Department, Reference Centre of Inherited Metabolic Diseases, Unidade Local de Saúde de S. José, Centro Clínico Académico de Lisboa, Portugal
2 - Neuropediatric Unit, Pediatric Department, Reference Centre of Inherited Metabolic Diseases, Unidade Local de Saúde de S. José, Centro Clínico Académico de Lisboa, Portugal
3 - Child Psychiatry Unit, Pediatric Department, Unidade Local de Saúde de S. José, Centro Clínico Académico de Lisboa, Portugal
4 - Nutrition Service, Reference Centre of Inherited Metabolic Diseases, Unidade Local de Saúde de S. José, Centro Clínico Académico de Lisboa, Portugal
5 - Dietary and Nutrition Service, Unidade Local de Saúde de S. Maria, Portugal
6 - NOVA Medical School, Universidade NOVA de Lisboa, Portugal
7 - CHRC – Comprehensive Health Research Centre, NOVA Medical School, Universidade NOVA de Lisboa, Portugal
8 - CINTESIS – Centre for Health Technology and Services Research, NOVA Medical School, Lisboa, Portugal
- Poster no Annual Symposium - Society For The Study Of Inborn Errors Of Metabolism, Porto, 20 de agosto a 3 de setembro de 2024
Resumo: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) (OMIM 616277) is a rare autosomal recessive disease that disturbs medium- and short-chain fatty acids b-oxidation and, valine and isoleucine catabolism. It leads to accumulation of toxic intermediates that disrupts pyruvate dehydrogenase (PDH) complex and mitochondrial respiratory chain, reducing ATP production. Patients can present with variable age of onset and a wide spectrum of clinical features the most common being severe encephalopathy and lactic acidosis during neonatal period with Leigh-like syndrome; developmental regression in infancy; and isolated paroxysmal dystonia exacerbated by illness or exertion. A valine- and fat-restricted diet is a rational approach, but evidence is limited.
Case 1: female, 7Y, presented at 10 M with horizontal nystagmus, truncal ataxia, axial hypotonia and dystonia. She had lactic acidosis with intercurrent illness and high urinary 2,3-dihydroxy-2-methylbutyric acid. MRI showed bilateral basal ganglia lesions. The exome showed 2 pathogenic mutations in ECHS1 gene. Despite valine-restricted diet and cofactors cocktail, she evolved with psycho-motor regression, dystonia and complete dependence on daily living activities.
Case 2: female, 16 Y presented at 4 Y with dystonic episodes triggered by physical exercise, fatigue or emotional stress, refractory to levodopa and benzodiazepines. MRI showed bilateral globus pallidus lesions. Molecular studies were negatives. Given the low lymphocyte PDH activity, ketogenic diet was started assuming the diagnosis of a PHD deficiency, with dramatic improvement in dystonic episodes. Subsequent exome reevaluation detected 2 pathogenic mutations in ECHS1. Recently, ketogenic diet has been gradually switched into a valine restricted diet.
Our cases illustrate variable clinical presentations and outcomes. More research is needed to understand how nutritional interventions can impact disease progression.