Teaching NeuroImage: A 6-Month-Old Boy With Arginine-Glycine Amidinotransferase Deficiency

Abstract: A 6-month-old boy born at term presented with global developmental delay and hypotonia. He had no history of seizure. Pregnancy, delivery, and family history were noncontributory. Serum creatine kinase (CK) was normal. Brain MRI (Figure, A and B) s showed diffusion restriction around the bilateral posterior horn of the lateral ventricles. T1 and T2-weighted MRI images were normal. Given concern for a metabolic etiology, blood and urine testing was sent, which revealed low levels of guanidinoacetate (GAA), creatine, and creatinine. MRS (Figure, C) showed decreased creatine peak, a hallmark of creatine deficiency disorders (CDDs). Trio- WGS identified pathogenic compound heterozygous variants in GATM (c.459T>G, exon1- 2del) supporting a diagnosis of arginine-glycine amidinotransferase (AGAT) deficiency. After 3 months of oral creatine supplementation and rehabilitation, developmental trajectory improved. AGAT deficiency is an autosomal recessive CDD1 characterized by intellectual disability (>80%), behavioral disorders (25%), seizure (10%), and muscle weakness/myopathy (50%).2 To date, there have only been 16 reported cases.

Link to article: https://www.neurology.org/doi/10.1212/WNL.0000000000213637

PubMed:  https://pubmed.ncbi.nlm.nih.gov/40397838/

Authors: Jun Duan

Key Terms: AGAT, Clinical Study, MRS, Mutation Study, Diagnostic, Pediatric Patient, Male Patient