[MIM 300 322, 308 950]

(Kelley-Seegmiller syndrome, complete deficiency in hypoxanthine-guanine-phosphoribosyltransferase, deficiency in hypoxanthine-guanine-phosphoribosyltransferase grade IV)

Rare. X-linked recessive transmission of a mutation of the  HPRT1 gene on Xq26. A few cases have been reported in girls. It is the most severe form of hypoxanthine-guanine-phosphoribosyltransferase (HPRT) deficiency: it causes a disturbance of the metabolism of purines with, typically,

-        hyperuricemia that responds to allopurinol; sandy urine in infants, risk of lithiasis

-        variable mental retardation

-        severe spasticity accompanied by choreo-dyskinetic movements: at rest, hypotonia and action dystonia that prevents  standing and walking; it is accompanied by sudden movements (ballism)

-        compulsive self-mutilation: biting of hands and perioral regions

There is often a megaloblastic anemia due to a relative folate deficiency .

The partial form of the deficiency is called Kelly-Seegmiller syndrome.

Abnormalities of dopaminergic neurotransmission at the level of the basal ganglia could be the origin of the movement disorders

There are 4 groups according to the severity of the symptoms:

-        group 1: no clear neurological symptoms but hyperuricemia with lithiasis and attacks of gout

-  group 2: moderate neurological signs: dystonia, dysarthria, mental retardation

-        group 3: severe neurological signs: no mental retardation but extremely debilitating dystonia

-        group 4: typical Lesch-Nyhan syndrome

Anesthetic implications:

difficult positioning and venous access. Risk of regurgitation and vomiting. Absence of adrenergic stress response. No specific anesthetic recommandations. A reported case of tracheal diverticulum resulting in difficult intubation .

References : 

-        Larson LO, Wilkins RG. 
Anesthesia and the Lesch-Nyhan syndrome. 
Anesthesiology 1985; 63:197-9.

-         Salhotra R, Sharma C, Tyagi A, Kumar S, Sethi AK, Bhatt S. 
An unanticipated difficult airway in Lesch-Nyhan syndrome. 
J Anaesth Clin Pharmacol 2012; 28: 239-41.

-         Torres RJ, Puig JG. 
Hypoxanthine-guanine-phosphoribosyltransférase (HPRT) deficiency : Lesch-Nyhan syndrome.
Orphanet J Rare Diseases 2007; 2 :48

Updated: February 2019