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Ethylmalonic encephalopathy
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Extremely rare. Autosomal recessive transmission of mutations of the ETHE1 gene (19q13.31) coding for a mitochondrial sulphide dioxygenase involved in the metabolism of hydrogen sulphide (H2S). The absence or dysfunction of this enzyme causes accumulation of H2S and thiosulphates in tissues. H2S inhibits the mitochondrial respiratory chain and the oxidation of the short-chain fatty acids, resulting in a clinical picture of:
- recurrent petechiae, and orthostatic acrocyanosis (damage of vessels)
- chronic diarrhea following hemorrhagic suffusions at the level of the intestinal mucosa
- delayed development with psychomotor regression,
- hypotonia
- abnormally high excretion of ethylmalonic acid
- at MRI: necrosis of parts of the grey matter.
The disease becomes apparent at birth or in the first months of life. Spastic paraplegia may be present. In addition to increased excretion of ethylmalonic acid, moderately increased quantities of methylsuccinic acid and C4C6 acylglycines can be found in the urine. In the blood: elevated levels of thiosulphates and major lactic acidosis.
In some patients, the results of urine and blood analyses can be similar to those obtained in case of type 2 glutaric aciduria (MAD deficiency or multiple acylCoA dehydrogenase deficiency, see this term). In other cases, they are similar to those observed in case of short chain acylCoA dehydrogenase deficiency (SCAD deficiency, see this topic).
The prognosis is generally poor: although there are less severe forms, most patients die before the age of 10 years.
Symptomatic treatment: L-carnitine, metronidazole (to decrease the bacterial production of H2S in the intestine) and N-acetyl-cysteine (to ensure a sufficient stock of intracellular glutathione).
A case report of liver transplantation has resulted in spectacular regression of the clinical and biological signs.
Anesthetic implications:
specific management for a mitochondrial cytopathy (see this topic); monitoring of blood glucose and lactates
References :
- Dionisi-Vici C, Diodato D, Torre G, Picca S, Pariante R et al.
Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.
Brain 2016; in press
Updated: June 2019