Guanidinoacetate methyltransferase (GAMT) deficiency: Outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring

被引：98

作者：

Stockler-Ipsiroglu, Sylvia ^{[1
]}

van Karnebeek, Clara ^{[1
,2
]}

Longo, Nicola ^{[3
]}

Korenke, G. Christoph ^{[4
]}

Mercimek-Mahmutoglu, Saadet ^{[5
]}

Marquart, Iris ^{[4
]}

Barshop, Bruce ^{[6
]}

Grolik, Christiane ^{[7
]}

Schlune, Andrea ^{[8
]}

Angle, Brad ^{[9
]}

Araujo, Helena Caldeira ^{[10
]}

Coskun, Turgay ^{[11
]}

Diogo, Luisa ^{[12
]}

Geraghty, Michael ^{[13
]}

Haliloglu, Goknur ^{[11
]}

Konstantopoulou, Vassiliki ^{[14
]}

Leuzzi, Vincenzo ^{[15
]}

Levtova, Alina ^{[16
]}

MacKenzie, Jennifer ^{[17
]}

Maranda, Bruno ^{[18
]}

Mhanni, Aizeddin A. ^{[19
]}

Mitchell, Grant ^{[16
,20
]}

Morris, Andrew ^{[21
]}

Newlove, Theresa ^{[1
]}

Renaud, Deborah ^{[22
]}

Scaglia, Fernando ^{[23
]}

Valayannopoulos, Vassili ^{[24
]}

van Spronsen, Francjan J. ^{[25
]}

Verbruggen, Krijn T. ^{[25
]}

Yuskiv, Nataliya ^{[1
]}

Nyhan, William ^{[6
]}

Schulze, Andreas ^{[5
,26
]}

机构：

[1] Univ British Columbia, Dept Pediat, Vancouver, BC V6H 3V4, Canada

[2] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V6H 3V4, Canada

[3] Univ Utah, Div Med Genet, Salt Lake City, UT USA

[4] Childrens Hosp Oldenburg, Dept Pediat Neurol, Oldenburg, Germany

[5] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5S 1A1, Canada

[6] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[7] Childrens Hosp Cologne, Dept Pediat Neurol, Cologne, Germany

[8] Univ Dusseldorf, Univ Childrens Hosp, Fac Med, Dept Gen Pediat Neonatol & Pediat Cardiol, Dusseldorf, Germany

[9] Childrens Mem Hosp, Div Birth Defects & Metab, Chicago, IL 60614 USA

[10] Univ Madeira, Unit Med Sci, Funchal, Madeira, Portugal

[11] Hacettepe Univ, Dept Pediat, Ankara, Turkey

[12] Pediat Hosp CHUC EPE, Coimbra, Portugal

[13] Univ Ottawa, Dept Pediat, CHEO, Ottawa, ON K1N 6N5, Canada

[14] Med Univ Vienna, Dept Pediat, Vienna, Austria

[15] Univ Roma La Sapienza, Dept Pediat Child Neurol & Psychiat, I-00185 Rome, Italy

[16] St Justine Univ Hosp Ctr, Dept Pediat, Montreal, PQ, Canada

[17] Queens Univ, Dept Pediat, Kingston, ON K7L 3N6, Canada

[18] Univ Sherbrooke, Div Genet, Sherbrooke, PQ J1K 2R1, Canada

[19] Univ Mannitoba, Dept Pediat & Child Hlth, Winnipeg, MB, Canada

[20] St Justine Univ Res Ctr, Montreal, PQ, Canada

[21] Manchester Acad Hlth Sci Ctr, Dept Med Genet, Manchester, Lancs, England

[22] Mayo Clin, Dept Neurol, Rochester, MN USA

[23] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[24] Hop Necker Enfants Malad, Reference Ctr Inborn Errors Metab, Paris, France

[25] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, NL-9700 AB Groningen, Netherlands

[26] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

来源：

MOLECULAR GENETICS AND METABOLISM | 2014年 / 111卷 / 01期

关键词：

Creatine deficiency; Magnetic resonance spectroscopy; Speech delay; Autism; Treatment evidence; Neurodevelopmental outcome; GLOBAL DEVELOPMENTAL DELAY; ARGININE RESTRICTION; CREATINE DEFICIENCY; INBORN ERROR; PRESYMPTOMATIC TREATMENT; INTELLECTUAL DISABILITY; MENTAL-RETARDATION; BRAIN; METABOLISM; ORNITHINE;

D O I：

10.1016/j.ymgme.2013.10.018

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We collected data on 48 patients from 38 families with guanidinoacetate methyltransferase (GAMT) deficiency. Global developmental delay/intellectual disability (DD/ID) with speech/language delay and behavioral problems as the most affected domains was present in 44 participants, with additional epilepsy present in 35 and movement disorder in 13. Treatment regimens included various combinations/dosages of creatine-monohydrate, L-ornithine, sodium benzoate and protein/arginine restricted diets. The median age at treatment initiation was 25.5 and 39 months in patients with mild and moderate DD/ID, respectively, and 11 years in patients with severe DD/ID. Increase of cerebral creatine and decrease of plasma/CSF guanidinoacetate levels were achieved by supplementation with creatine-monohydrate combined with high dosages of t-ornithine and/or an arginine-restricted diet (250 mg/kg/d L-arginine). Therapy was associated with improvement or stabilization of symptoms in all of the symptomatic cases. The 4 patients treated younger than 9 months had normal or almost normal developmental outcomes. One with inconsistent compliance had a borderline IQ at age 8.6 years. An observational GAMT database will be essential to identify the best treatment to reduce plasma guanidinoacetate levels and improve long-term outcomes. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

引用

页码：16 / 25

页数：10

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