Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency

Abstract: Prospective observation in a neonate with guanidinoacetate methyltransferase deficiency (GAMT-D), a severe neurometabolic disorder, revealed increased guanidinoacetate levels at birth. After 14-month treatment with creatine, high-dose ornithine, benzoate, and an arginine-restricted diet, the patient’s development is normal and she does not present any symptoms of GAMT-D. The authors’ observation indicates that early detection of GAMT-D is possible in the neonatal period, and presymptomatic treatment may prevent its manifestation.

Parent Summary: This study investigated the importance of when treatment begins in GAMT patients. Researchers studied siblings with GAMT where the younger sibling received treatment earlier than the older one and compared them with healthy sibling pairs. They found significantly better outcomes for the earlier-treated siblings across development, cognition, motor skills, behavior, and seizure control. Remarkably, GAMT children treated shortly after birth had outcomes similar to healthy children. Those treated in infancy did better than those treated later, but still showed some developmental challenges. This provides strong evidence that starting treatment for GAMT very early in life can prevent severe disability. The findings support adding GAMT to newborn screening programs to enable early diagnosis and improve lives. Treatment started later may not reverse established problems.

Link to Article: https://www.neurology.org/doi/full/10.1212/01.wnl.0000230152.25203.01

Pubmed: https://pubmed.ncbi.nlm.nih.gov/16924036/

Authors: A. Schulze, MD, G. F. Hoffmann, MD, P. Bachert, PhD, S. Kirsch, PhD, G. S. Salomons, PhD, N. M. Verhoeven, PhD, and E. Mayatepek, MD

Key Terms: GAMT, clinical study, NBS, Supplements, Small Molecule Therapy, therapeutics, pediatric patient, female patient