[Analysis of clinical features and genetic variants in a child with creatine deficiency syndrome]

To explore the clinical features and genetic basis for a patient diagnosed with creatine deficiency syndrome (CDS).

The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. The level of creatine was determined by using a magnetic resonance spectrum (MRS) method.

The patient presented with development delay and poor response to stimuli. No obvious abnormality was found with his muscle tone and strength of his limbs. Borderline EEG was detected. MRI showed abnormal development of the white matter and dysplasia of corpus callosum. Urine organic acid screening has shown increased glycerin-3-phosphate. WES revealed that the patient has carried compound heterozygous variants of the GAMT gene, namely c.412C>T and IVS4-1G>A, which were respectively derived from his mother and father. MRS showed reduced creatine in bilateral basal ganglia. Functional study of the splicing site suggested that the IVS4-1G>A variant has resulted skipping of exon 5 upon splicing.

The compound variants of the GAMT gene probably underlay the disease in this child. Above finding has enriched the spectrum of GAMT gene variants.