Apatean, D

Battini, R

Debrosse, S

Dessoffy, K

Dowling, Md

Edvardson, S

Eichler, F

Johnston, K

Koeller, Dm

Nouioua, S

Stockler-Ipsiroglu, S

Tazir, M

Verma, A

Wierenga, Am

Wierenga, Kj

Wong, Lc

Zhang, V

Background: Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis.

Objective: We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition.

Results: 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations.

Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions.

Conclusion: AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GM and cerebral creatine levels (via brain MRS), and by GATM gene sequencing

Stockler-Ipsiroglu S

Apatean D

Battini R

DeBrosse S

Dessoffy K

Edvardson S

Eichler F

Johnston K

Koeller DM

Nouioua S

Tazir M

Verma A

Dowling MD

Wierenga KJ

Wierenga AM

Zhang V

Wong LC

Archivio della Ricerca - Università di Pisa

English

Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide

Arginine: glycine amidinotransferase /AGAT) deficiency: clinical features and long term outcomes in 16 patient diagnosed worldwide

Arginine: glycine amidinotransferase /AGAT) deficiency: clinical features and long term outcomes in 16 patient diagnosed worldwide

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Archivio della Ricerca - Università di Pisa