An incidental finding in newborn screening leading to the diagnosis of a patient with ECHS1 mutations
| Autor: | Sonia Pajares, J. Garcia-Villoria, Laura Gort, Ana Argudo-Ramírez, Olatz Ugarteburu, J.M. González De Aledo-Castillo, Antonia Ribes, J. A. Arranz, Frederic Tort, R.M. López, M.D. Casellas, Raúl Debesa Fernández, José Luis Marín, M. del Toro |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Newborn screening
Pediatrics medicine.medical_specialty C3DC malonylcarnitine Tiglylcarnitine Genetic counseling 2-methyl-2 3-dihydroxybutyric acid Case Report ECHS1 deficiency Disease Congenital lactic acidosis TMS trimethylsilyl ECHS1 short-chain enoyl-CoA hydratase 3MGA 3-methylglutaconic acid Endocrinology Mutations in ECHS1 Genetics medicine HIBCH 3-hydroxy-isobutyryl-CoA hydrolase Molecular Biology Exome lcsh:QH301-705.5 C4OH 3-hydroxy-butyrylcarnitine\3-hydoxy-isobutyrylcarnitine DBS dried blood spot Dystonia lcsh:R5-920 business.industry medicine.disease PDH pyruvate dehydrogenase C5:1 tiglylcarnitine NBS Newborn Screening lcsh:Biology (General) MS mass spectrometry 3-hydroxy-butyrylcarnitine\3-hydoxy-isobutyrylcarnitine Hypertonia medicine.symptom DUS dried urine spot business lcsh:Medicine (General) GC gas chromatography MRI magnetic resonance imaging Cutis laxa |
| Zdroj: | Molecular Genetics and Metabolism Reports Molecular Genetics and Metabolism Reports, Vol 22, Iss, Pp-(2020) |
| ISSN: | 2214-4269 |
| Popis: | Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters, as well as in valine metabolism. ECHS1 deficiency has multiple manifestations, including Leigh syndrome early at birth or in childhood with poor prognosis, to cutis laxa, exercise-induced dystonia and congenital lactic acidosis.Here we describe the case of a newborn with mutations in ECHS1 that caught our attention after the incidental finding of 3-hydroxy-butyryl/3-hydroxy-isobutyryl/malonylcarnitine (C4OH/C3DC) and tiglylcarnitine (C5:1) on blood spot in the newborn screening (NBS) program. Diagnosis was suspected based on the analysis of organic acids on dried urine spot. A moderate increase of 2-methyl-2,3-dihydroxybutyric acid, was detected, which is a known marker of this disease. Exome analysis showed c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene. The child was therefore admitted to the hospital. Initial examination showed little response to auditory stimuli and mild hypertonia of the extremities. Clinical deterioration was evident at 4 months of age, including neurological and cardiac involvement, and the patient died at 5 months of age. This case illustrates how an incidental detection in the NBS Program can lead to the diagnosis ECHS1 deficiency. Although it is a severe disease, with no treatment available, early detection would allow adequate genetic counseling avoiding the odyssey that suffered most of these families. Keywords: ECHS1 deficiency, Mutations in ECHS1, Newborn screening, 2-methyl-2,3-dihydroxybutyric acid, 3-hydroxy-butyrylcarnitine/3-hydoxy-isobutyrylcarnitine, Tiglylcarnitine |
| Databáze: | OpenAIRE |
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