[MIM 259 900]

(Primary hyperoxaluria type I, glycolic aciduria, hyperglycolaturie)

Rare: 1/120.0000 live births in France, but more frequent in areas where consanguinity  is important It is the most common form of primary hyperoxaluria (80%). The term 'oxalosis' refers to a thesaurismosis of Ca oxalate.

Autosomal recessive transmission of a mutation of the AGXT gene (2q36-q37) which results in a deficiency in alanine glyoxylate aminotransferase (AGT) that transforms glyoxalate to glycine of hepatocytes. The accumulation of oxalate in the kidneys leads to early renal failure, usually before the age of 15 years. The Hyperoxaluria is associated with a hyperglycolaturia.

The first symptoms appear in 2/3 of the cases before the age of 5 years, and are caused by urolithiasis :  infections, hematuria or urinary tract obstruction. Nephrocalcinosis appears early. End stage renal failure occurs before the age of 15 in almost half of cases. In 10 % of cases (infantile form), renal failure appear in the first year of life; in these cases, ultrasound and radiography show already almost completely calcified kidneys (diffuse nephrocalcinosis).

Due to renal failure, oxalate builds up in tissues

-        cornea

-        bones: accumulation of oxalates in metaphyseal areas; the bones become fragile with spontaneous fractures that consolidate with difficulty

-        heart: disorders of cardiac conduction, systemic hypertension, cardiomyopathy

-        vessels: arteritis of the limbs (oxalate crystals in the media)

-        joints: painful stiffness, resulting in a bedridden status

-        skin and oral mucous membranes: subcutaneous or submucosal crystals.

Treatment includes :  abundant drinks, an alkalinization of the urine; pyridoxine (vitamin B6: 5 to 20 mg/kg), the coenzyme of AGT, can be useful in case of G170R mutation (20 to 30 % of cases).

New therapeutic approach: subcutaneous Lumasiran (1x/month for the first 3 doses and every 3 months thereafter). It reduces drastically the oxalates blood level as well as the oxaluria.

Single kidney transplantation is performed when glomerular filtration rate is still over 40 ml/min; however oxalose reccurs as oxalate builds up on the graft and destroys it, except in a minority of cases (G170R mutation ) where vitamin B6 (pyridoxine) partially corrects the enzyme deficiency.

The only curative treatment (current indications: form infant or glomerular filtration rate less than 20 ml/min) is combined liver and kidney transplantation. To avoid loosing the renal graft or even cardiac failure following massive precipitation of oxalate  caused by the recirculation of oxalate accumulated in the tissues, it is important to hemodialyze the child just before liver transplantation, and often following it aiming at oxalate blood levels < 30 µM/L after dialysis. If oxalate levels remain high, it is better to perform kidney transplantation after and away from liver transplantation

Anesthetic implications:

kidney failure often with partly preserved diuresis: perioperative hyperhydration. ECG (conduction disorders ?) and echocardiography (cardiomyopathy ?).

A case  of transient hepatitis following a sevoflurane anesthesia has been reported: chance association ? promoting role of renal failure ?

References : 

-         Reich A, Schulze Everding A, Bulla M, Brinkmann OA, Van Aken H. 
Hepatitis after sevoflurane exposure in an infant suffering from primary hyperoxaluria type I.
Anesth Analg 2004; 99: 370-2.

-         Gagnadoux M-F, 
Primary hyperoxaliuria. 
EMC-Pédiatrie 2004 : 45-50.

-         Madan N, Arnon R, Arnon R. 
Evaluation of cardiac manifestations in pediatric liver transplantation candidates. 
Pediatr Transplantation 2012; 16: 318-28.

-         Benhenda N, Bernard-Brunet A, Ferrandière M, Salamé E, Babuty D. 
Fatal short-coupled torsade de points in a patient with primary oxalosis. 
Intensive Care Med 2013; 39: 1843-4.

-        Ganschow R, Hoppe B. 
Review of combined liver and kidney transplantation in children. 
Pediatr Transplant 2015; 19:820-6.

Updated: January 2021