Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase Deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase.

Background: Guanidinoacetate methyltransferase deficiency (GAMT) is an autosomal recessive inborn error of metabolism. A condition that results from a pathogenic variant in the GAMT gene that maps to 19p13.3. The prevalence can be estimated to be up to 1:2,640,000 cases; countries such as Saudi Arabia could have a higher prevalence due to high consanguinity rates. The clinical manifestations that a patient could obtain are broad and start to manifest in the patients' early childhood years.

Materials and methods: A thorough review of case reports in January 2022 was conducted. The retrieved literature was screened for demographic data. Patients of all ages were included. Qualitative variables were described as number and percentage (%), and quantitative data were described by the mean and standard deviation. In bivariate data, Chi-square test (χ²) was used and t-test for nonparametric variables.

Results: Gender distribution was 53% of males and 47% females. Reported age ranged from 8 to 31 months. At the age of onset, 50% of the cases were infants, 28% were toddlers, and 15% were children, concluding that 79% of the reported cases developed symptoms before 5 years old. 68% of the cases developed generalized seizures throughout their life. 84% of the cases expressed a form of developmental delay. 43% of the cases had intellectual disabilities and mental retardation that affected their learning process; most cases required special care. 23% of the affected cases were of consanguineous marriages, and 7% had affected relatives.

Conclusion: We described four novel case reports, the first to be reported in Saudi Arabia. Seizure was a leading finding in the majority of the cases. Developmental delay was broadly observed. Intellectual delay and language impairments are primary hallmarks. Further understanding and early diagnosis are recommended. Premarital testing of neurogenetic diseases using whole-exome sequencing is probably a future direction, especially in populations with high consanguinity rates.