Paroxysmal exercise-induced dystonia within the phenotypic spectrum of<i>ECHS1</i>deficiency

Olgiati, Simone; Škorvánek, Matej; Quadri, Marialuisa; Minneboo, Michelle; Graafland, Josja; Breedveld, Guido J.; Bonte, Ramon; Özgür, Zeliha; Hout, Mirjam C G N van den; Schoonderwoerd, Kees; Verheijen, Frans W.; IJcken, Wilfred F. J. van; Chien, Hsin Fen; Barbosa, Egberto Reis; Chang, Hsin-Yu; Lai, Shen‐Hao; Yeh, Tu Hsueh; Lu, Chin Song; Wu-Chou, Yah Huei; Kievit, Anneke J.A.; Haň, Vladimír; Gdovinová, Zuzana; Jech, Robert; Hofstra, Robert M.W.; Ruijter, George J. G.; Mandemakers, Wim; Bonifati, Vincenzo

doi:10.1002/mds.26610

Cited by 61 publications

(85 citation statements)

References 25 publications

(96 reference statements)

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“…To date, almost half of cases diagnosed with this autosomal recessive disorder perish within the neonatal or infantile period, but survival into adulthood is reported. To date, at least 20 missense exonic, one nonsense, and a few splice site and frame shift mutations in ECHS1 have been reported associated with this relatively novel disorder [5, 8–13, 15–17]. …”

Section: Introductionmentioning

confidence: 99%

Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency

Bedoyan

Yang

Ferdinandusse

et al. 2017

Molecular Genetics and Metabolism

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Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and CSF lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid was markedly elevated as were metabolites of the three branched-chain ketoacids on urine organic acids analysis. These urine metabolites notably decreased when lactic acidosis decreased in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity was deficient, but PDC and α-ketoglutarate dehydrogenase complex activities in cultured fibroblasts were normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts was suggestive of slightly reduced PDC activity relative to control range in mitochondria. We reviewed 16 other cases with mutations in ECHS1 where PDC activity was also assayed in order to determine how common and generalized secondary PDC deficiency is associated with primary SCEH deficiency. For reasons that remain unexplained, we find that about half of cases with primary SCEH deficiency also exhibit secondary PDC deficiency. The patient died on day-of-life 39, prior to establishing his diagnosis, highlighting the importance of early and rapid neonatal diagnosis because of possible adverse effects of certain therapeutic interventions, such as administration of ketogenic diet, in this disorder. There is a need for better understanding of the pathogenic mechanisms and phenotypic variability in this relatively recently discovered disorder.

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Section: Introductionmentioning

confidence: 99%

Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency

Bedoyan

Yang

Ferdinandusse

et al. 2017

Molecular Genetics and Metabolism

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“…It is worthy of note that all patients described so far have pallidal hyperintensity on T2-MRI sequences (despite being very mild in one patient with isolated PED,29 suggesting this might be a clue to suspect ECHS1 mutations. A possible benefit with ketogenic diet or a mitochondrial cocktail including thiamine, riboflavin, carnitine, coenzyme Q-10, vitamin B 6 and vitamin C has been reported in PxD 28 30…”

Section: Disorders Presenting With Pxdmentioning

confidence: 93%

Unravelling of the paroxysmal dyskinesias

Erro

Bhatia

2018

J Neurol Neurosurg Psychiatry

108

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Paroxysmal dyskinesias (PxD) refer to a rare group of clinically and genetically heterogeneous disorders presenting with recurrent attacks of abnormal movements, typically dystonia, chorea or a combination thereof, without loss of consciousness. Classically, PxD have been categorised according to their triggers and duration of the attacks, but increasing evidence suggests that there is a certain degree of clinical and genetic overlap and challenges the concept that one phenotype is attributable to one single aetiology. Here we review the increasing spectrum of genetic conditions, as well as of other non-genetic disorders, that might present with PxD, provide criteria for case definition and propose a diagnostic workup to reach a definitive diagnosis, on which treatment is heavily dependent.

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“…[1][2][3][4][5][6][7][10][11] There are many forms of Paroxysmal Dystonia/Dyskinesia, but there are only a few that are ever diagnosed which are Paroxysmal Kinesigenic Dystonia (PKD), Paroxysmal Non-kinesigenic Dystonia (PNKD), and Paroxysmal Exercise-induced Dystonia (PED). The most common out of the three is PKD.…”

Section: Related Literaturementioning

confidence: 99%