[MIM 260 005]

(5-oxoprolinase deficiency)

Anomaly  of the γ-glutamyles cycle playing a role in the synthesis of glutathione.

Primary form : very rare. Autosomal recessive transmission. Unknown gene. Important urinary excretion of 5-oxoproline but normal cellular levels of glutathione.

Secondary forms: occurs sometimes in very preterm babies; the described cases are due to inhibition of one of the enzymes of the γ-glutamyles cycle, for example,

- depletion of glutathione by large doses of paracetamol

- inhibition of 5-oxoprolinase by an antibiotic (flucloxacillin, netimicine) or vigabatrin

- some cases of homocystinuria, cystinosis, tyrosinemia, or ornithine carbamyl transferase deficiency

- severely burned patient or Stevens-Johnson Syndrome

- malnutrition or pregnancy (glycine deficiency).

These secondary forms are reversible and usually produce major metabolic acidosis with an increased anion gap .

An important 5-oxoprolinuria is also found in case of moderate or severe glutathione synthetase (20q11.2) deficiency (see that term).

Anesthetic implications : 

secondary forms: correction of the metabolic acidosis

References : 

-        Ristoff E, Larsson A, Jaeken J. 
Disorders in the metabolism of glutathione and imidazole dipeptides. p 375-80, 
in Inborn Metabolic Diseases by Fernandes J, Saudubray J-M, van den Berghe G, Walter JH, 4th ed, Springer 2006.

-        Veldhuijzen N, Kamphuis S, van den Bergh F, Spronk P, Braber A. 
Madam, why are you so sour ? 
Eur J Anaesthesiol 2012; 29: 398-400.

Updated December 2019