Ethylmalonic encephalopathy

An autosomal recessive severe metabolic disorder of infancy affecting the brain, gastrointestinal tract, and peripheral vessels. The disorder is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae (PURPURA), orthostatic acrocyanosis, and chronic diarrhea. Brain MRI shows necrotic lesions in deep gray matter structures. Death usually occurs in the first decade of life. Mutations in the ETHE1 gene have been identified. OMIM: 602473

Also Known As:

Networked: 66 relevant articles (3 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Mitochondrial Diseases (Mitochondrial Disease)
2.	Purpura
3.	Brain Diseases (Brain Disorder)
4.	Short chain Acyl CoA dehydrogenase deficiency
5.	Metabolic Diseases (Metabolic Disease)

Experts

1.	Zeviani, Massimo: 12 articles (12/2020 - 02/2004)
2.	Tiranti, Valeria: 10 articles (12/2020 - 02/2004)
3.	Wajner, Moacir: 8 articles (04/2022 - 02/2009)
4.	Di Meo, Ivano: 7 articles (01/2021 - 02/2009)
5.	Viscomi, Carlo: 7 articles (04/2016 - 02/2009)
6.	Leipnitz, Guilhian: 6 articles (04/2022 - 01/2012)
7.	Palmfeldt, Johan: 5 articles (01/2019 - 05/2011)
8.	Grings, Mateus: 4 articles (04/2022 - 02/2010)
9.	Amaral, Alexandre Umpierrez: 4 articles (01/2017 - 01/2012)
10.	Schuck, Patrícia Fernanda: 4 articles (01/2015 - 02/2009)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Ethylmalonic encephalopathy:

1.	Acetylcysteine (Siran)FDA LinkGeneric 01/01/2017 - "Successful treatment of a patient with ethylmalonic encephalopathy by intravenous N-acetylcysteine." 08/01/2010 - "Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy."
2.	Metronidazole (Metric)FDA LinkGeneric 08/01/2010 - "Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy."
3.	Riboflavin (Vitamin B2)FDA LinkGeneric 12/01/2001 - "Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin." 12/01/2001 - "The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful."
4.	CopperIBA 01/01/2003 - "In this study, we test the possibility that defective copper uptake or intracellular translocation represents the basic defect in three categories of candidate phenotypes among 22 patients: ethylmalonic encephalopathy; mitochondriopathies of unknown aetiology; and neurodevelopmental abnormalities with clinical and chemical evidence of copper deficiency. " 01/01/2003 - "Mutation analysis of copper transporter genes in patients with ethylmalonic encephalopathy, mitochondriopathies and copper deficiency phenotypes."
5.	Sulfides (Thioethers)IBA 01/01/2014 - "Mutations in ETHE1 causing loss of function result in sulfide toxicity and in the rare fatal disease Ethylmalonic Encephalopathy (EE). " 01/01/2013 - "Altered sulfide (H(2)S) metabolism in ethylmalonic encephalopathy." 05/01/2015 - "Mutations to the hETHE1 gene compromise sulfide metabolism leading to the genetic disease ethylmalonic encephalopathy. " 01/01/2017 - "Hydrogen sulfide (sulfide) accumulates at high levels in brain of patients with ethylmalonic encephalopathy (EE). " 07/25/2013 - "In patients suffering from EE (ethylmalonic encephalopathy), a block in sulfide oxidation at the level of the SDO (sulfur dioxygenase) ETHE1 leads to severe dysfunctions in microcirculation and cellular energy metabolism. "
6.	Proteins (Proteins, Gene)FDA Link 02/01/2004 - "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein." 10/01/2021 - "Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma." 06/18/2019 - "Ethylmalonic Encephalopathy Protein 1 (ETHE1) is a sulfur dioxygenase that regulates cellular H2S levels. " 11/11/2016 - "Persulfide dioxygenase (also called ethylmalonic encephalopathy protein 1, ETHE1) reportedly metabolizes GSSH to GSH with simultaneous oxygen consumption. " 11/11/2016 - "Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1."
7.	sulfur dioxygenaseIBA 10/28/2020 - "Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder caused by impaired mitochondrial sulfur dioxygenase. " 07/15/2011 - "Ethylmalonic encephalopathy (EE) is an autosomal recessive, invariably fatal disorder associated with mutations in ETHE1, a gene encoding a mitochondrial sulfur dioxygenase (SDO). " 01/01/2019 - "Ethylmalonic encephalopathy (EE) is a rapidly progressive autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the ETHE1 gene that encodes the mitochondrial sulfur dioxygenase. " 04/01/2022 - "Ethylmalonic encephalopathy (EE) is a severe intoxication disorder caused by mutations in the ETHE1 gene that encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide. " 06/18/2019 - "Ethylmalonic Encephalopathy Protein 1 (ETHE1) is a sulfur dioxygenase that regulates cellular H2S levels. "
8.	ethylmalonic acid (ethylmalonate)IBA 01/01/2021 - "Tissue accumulation and high urinary excretion of ethylmalonic acid (EMA) are found in ethylmalonic encephalopathy (EE), an inherited disorder associated with cerebral and cerebellar atrophy whose pathogenesis is poorly established. " 01/01/2015 - "Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. " 08/01/2014 - "Predominant accumulation of ethylmalonic acid (EMA) in tissues and biological fluids is a characteristic of patients affected by short chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy. " 03/01/2013 - "Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short-chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. " 09/01/2012 - "Mutations in human (Homo sapiens) ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 (ETHE1) result in the complex metabolic disease ethylmalonic encephalopathy, which is characterized in part by brain lesions, lactic acidemia, excretion of ethylmalonic acid, and ultimately death. "
9.	DioxygenasesIBA 01/01/2016 - "Defects in the gene encoding the persulfide dioxygenase ETHE1 are known to cause the severe inherited metabolic disorder ethylmalonic encephalopathy (EE). " 05/01/2015 - "Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy." 11/11/2016 - "Persulfide dioxygenase (also called ethylmalonic encephalopathy protein 1, ETHE1) reportedly metabolizes GSSH to GSH with simultaneous oxygen consumption. " 11/11/2016 - "Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1." 07/28/2015 - "Here, we show that CstB is a multifunctional Fe(II)-containing persulfide dioxygenase (PDO), analogous to the vertebrate protein ETHE1 (ethylmalonic encephalopathy protein 1). "
10.	Hydrogen Sulfide (Sulfide, Hydrogen)IBA 09/01/2012 - "Ethylmalonic encephalopathy (EE) is an invariably fatal disease, characterized by the accumulation of hydrogen sulfide (H(2)S), a highly toxic compound. " 01/01/2018 - "Ethylmalonic encephalopathy (EE) is a devastating neurodegenerative disease caused by mutations in the ETHE1 gene critical for hydrogen sulfide (H2S) detoxification. " 01/01/2017 - "Bioenergetics dysfunction, mitochondrial permeability transition pore opening and lipid peroxidation induced by hydrogen sulfide as relevant pathomechanisms underlying the neurological dysfunction characteristic of ethylmalonic encephalopathy." 04/01/2022 - "Ethylmalonic encephalopathy (EE) is a severe intoxication disorder caused by mutations in the ETHE1 gene that encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide. " 01/01/2017 - "Hydrogen sulfide (sulfide) accumulates at high levels in brain of patients with ethylmalonic encephalopathy (EE). "

Therapies and Procedures

1.	Liver Transplantation 04/01/2016 - "Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease." 01/01/2019 - "Improved clinical outcome following liver transplant in patients with ethylmalonic encephalopathy." 01/01/2021 - "Ethylmalonic encephalopathy and liver transplantation: long-term outcome of the first treated patient." 10/28/2020 - "Compromised therapeutic value of pediatric liver transplantation in ethylmalonic encephalopathy: A case report." 04/01/2016 - "Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. "
2.	Therapeutics 12/01/2020 - "Ethylmalonic encephalopathy: Clinical course and therapy response in an uncommon mild case with a severe ETHE1 mutation." 01/01/2022 - "This review summarizes the preclinical findings of AAV vector-based gene replacement therapy for mitochondrial diseases including Leigh syndrome, Barth syndrome, ethylmalonic encephalopathy, and others."