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.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

Dystonia is a symptom defined by involuntary and irregular contractions of the muscles, which cause movement disorders and postural problems. Deep brain stimulation (DBS) in globus pallidus interna (GPi) is a good option for controlling dystonia. DBS has already been shown to have significant effects on primary dystonia as well as Parkinson's disease. Dystonia is very difficult to manage, as seen in cerebral palsy (CP) mixed with spasticity. As CP patients grow, their musculoskeletal problems may require orthopedic surgery. However, the outcome of orthopedic surgery is not usually suitable due to dystonia. Therefore, we attempted to control dystonia through DBS initially and perform orthopedic surgery to correct musculoskeletal deformities after treatment of dystonia. Herein, we report a case that showed remarkable improvement in terms of the dystonia rating scale and gait pattern after combined therapy of DBS and orthopedic surgery.
Cerebral Palsy ; Congenital Abnormalities ; Contracts ; Deep Brain Stimulation ; Dystonia ; Dystonic Disorders ; Gait ; Globus Pallidus ; Humans ; Movement Disorders ; Muscle Spasticity ; Muscles ; Orthopedics ; Parkinson Disease