Secondary creatine deficiency in ornithine delta-aminotransferase deficiency.
OBJECTIVE
Ornithine delta-aminotransferase (OAT) deficiency causes gyrate atrophy (GA) of the retina, as a consequence of high plasma ornithine concentrations. Because creatine synthesis requires the conversion of arginine and glycine into ornithine and guanidinoacetate, high ornithine concentration inhibits this reaction thus causing secondary creatine deficiency. The aim of this study was to evaluate the neuropsychological features and creatine metabolism in patients with GA.


METHODS
The study involved 7 GA patients, aged from 11 to 27 years who underwent neuropsychological evaluation and cerebral proton magnetic resonance spectroscopy (MRS).


RESULTS
Neurocognitive impairment was found in 5/7 patients, including mental retardation (3/7), school failure (1/7), major visuospatial dyspraxia (1/7), aggressive behavior (3/7) and epilepsy (2/7). Two patients had normal neuropsychological evaluation. Cerebral proton magnetic resonance spectroscopy revealed a profound creatine deficiency in all patients. MRS data were confirmed by decreased levels of creatine and/or guanidinoacetate in plasma and urine in all patients.


CONCLUSIONS
In our group of patients with GA, we found a high prevalence of neurological impairment, not reported so far, and possibly related to secondary creatine deficiency and hyperornithinemia. We propose to treat mentally retarded GA patients with high doses of creatine, as it may normalize brain creatine levels and help to reduce ornithine levels.
Reference Center for Metabolic Disorders, Necker - Enfants Malades Hospital and Université Paris Descartes, 149 rue de Sèvres, 75015 Paris, France. vassili.valaya@nck.aphp.fr
V
V
Valayannopoulos
N
N
Boddaert
K
K
Mention
G
G
Touati
V
V
Barbier
A
A
Chabli
F
F
Sedel
J
J
Kaplan
J L
JL
Dufier
David
D
Seidenwurm
D
D
Rabier
J M
JM
Saudubray
P
P
de Lonlay
D000293:Adolescent; D000328:Adult; D000374:Aggression; D001072:Apraxias / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002648:Child; D003401:Creatine / Q000172:deficiency*; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism; D005260:Female; D015799:Gyrate Atrophy / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors / Q000172:deficiency*; D012189:Retrospective Studies; D055815:Young Adult
D009953:Ornithine-Oxo-Acid Transaminase; D003401:Creatine