Two cases of creatine deficiency syndrome caused by GAMT gene mutations and literature review

ZHAO Ting-Ting; PAN Zou; ZHONG Jian-Min; TANG Hai-Yun; YIN Fei; PENG Jing; CHEN Chen

doi:10.7499/j.issn.1008-8830.2411062

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Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (3) : 340-346. DOI: 10.7499/j.issn.1008-8830.2411062

CLINICAL RESEARCH

Two cases of creatine deficiency syndrome caused by GAMT gene mutations and literature review

ZHAO Ting-Ting, PAN Zou, ZHONG Jian-Min, TANG Hai-Yun, YIN Fei, PENG Jing, CHEN Chen

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Abstract

Objective To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. Methods A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. Results The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. Conclusions GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.

Key words

Creatine deficiency syndrome / GAMT gene / Intellectual disability / Epilepsy / Gene mutation / Child

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ZHAO Ting-Ting, PAN Zou, ZHONG Jian-Min, TANG Hai-Yun, YIN Fei, PENG Jing, CHEN Chen. Two cases of creatine deficiency syndrome caused by GAMT gene mutations and literature review[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(3): 340-346 https://doi.org/10.7499/j.issn.1008-8830.2411062

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