Two Cases of Creatine Deficiency Syndrome Caused by GAMT Gene Mutations and Literature Review

Abstract: Objectives: 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.

Link to article: https://pubmed.ncbi.nlm.nih.gov/40105081/

PubMed:  https://pubmed.ncbi.nlm.nih.gov/40105081/

Authors: Tingting Zhao, Zou Pan, Jianmin Zhong, Haiyun Tang, Fei Yin, Jing Peng, Chen Chen

Key Terms: GAMT, Clinical Study, MRS, Mutation Study, Diagnostic, Pediatric Patient, Male + Female Patient