Fernandes-Pires · Molecular genetics and metabolism 2022 · narrative review · n=?

Current and potential new treatment strategies for creatine deficiency syndromes.

Cited 72 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review without primary clinical data or systematic search methodology

PubMed 34972654 · doi:10.1016/j.ymgme.2021.12.005 · record verified 2026-08-26

What was done

The authors reviewed literature on creatine metabolism and creatine deficiency syndromes caused by mutations in GATM, GAMT, and SLC6A8, evaluating current clinical management approaches and emerging therapeutic strategies.

What was found

AGAT and GAMT deficiencies can be treated with high-dose oral creatine supplementation because the SLC6A8 transporter remains functional at the blood-brain barrier. In contrast, existing treatment strategies for creatine transporter deficiency benefit approximately one-third of patients and do not completely reverse the clinical phenotype. The abstract reports no specific quantitative outcomes or statistical metrics.

Why it matters

This review highlights the critical treatment gap between enzymatic creatine synthesis disorders and transporter deficiency, emphasizing the necessity of novel therapeutics capable of bypassing the defective SLC6A8 blood-brain barrier transport mechanism.

Limits

This is a narrative review with no original data, systematic search protocol, or meta-analysis reported in the abstract. Specific criteria defining treatment benefit, underlying sample sizes, and detailed intervention protocols were not provided.

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