# What are Creatine Deficiency Syndromes?
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This article addresses a health topic. It is not intended for self-diagnosis and should not replace a doctor's diagnosis. Please read our general and medical disclaimer.
# Creatine
Creatine is a nitrogen-containing compound stored in almost all body cells and serves as a quickly available energy reservoir. Creatine is essential for providing readily available adenosine triphosphate (ATP) in body cells. It plays a central role in energy metabolism, especially during short-term, intense physical exertion. Creatine is not only important for muscles but also for the brain. It functions as a fast energy store and likely plays a crucial role as a neurotransmitter in brain and nerve pathways. The human body requires about 2 grams of creatine per day. This amount is supplied approximately 50% through diet and 50% is produced enzymatically by the kidneys and liver.
# Endogenous Creatine Production
Creatine is produced in the body through a three-step process:
- The enzyme L-Arginine: Glycine-Amidinotransferase (AGAT) splits arginine from food in the kidneys and produces guanidinoacetate (GAA).
- The enzyme Guanidinoacetate Methyltransferase (GAMT) uses GAA to synthesize creatine in the liver.
- In the bloodstream, creatine is transported to the body's cells. It is absorbed at the cell walls via creatine transporters and is available for energy metabolism, e.g., for muscle and brain cells.
# Types of Creatine Deficiency Syndromes
There are three types of creatine deficiency syndromes:
| AGAT | GAMT | CTD |
|---|---|---|
| L-Arginine: Glycine-Amidinotransferase (AGAT) Deficiency | Guanidinoacetate Methyltransferase (GAMT) Deficiency | Creatine Transporter Defect (CTD) |
# L-Arginine: Glycine-Amidinotransferase (AGAT) Deficiency
Mutations in the AGAT gene lead to defective synthesis of L-Arginine: Glycine-Amidinotransferase. As a result, no endogenous creatine can be produced.
AGAT patients typically show less severe symptoms compared to GAMT and CTD patients because they have functioning transporters and can utilize naturally occurring creatine in the diet.
Treatment with oral creatine monohydrate supplementation is effective in meeting the body's creatine needs and greatly improves prognosis when started early in AGAT deficiency patients. Dietary restrictions are generally not recommended for AGAT patients.
# Guanidinoacetate Methyltransferase (GAMT) Deficiency
Mutations in the GAMT gene lead to a deficiency of Guanidinoacetate Methyltransferase.
Due to the lack of the GAMT enzyme, patients cannot break down guanidinoacetate (GAA), which is produced in the first step of creatine synthesis. This results in the accumulation of GAA, which becomes neurotoxic in high concentrations.
Treatment aims to reduce GAA production and provide the creatine that the body cannot produce. Patients are usually prescribed oral supplements of creatine monohydrate and L-ornithine. Some doctors also recommend dietary restrictions and supplementation with sodium benzoate to further minimize GAA accumulation.
# Creatine Transporter Defect (CTD)
CTD stands for Creatine Transporter Defect (English: Creatine Transporter Deficiency).
CTD is also referred to as SLC6A8 deficiency, CRTR, and X-linked creatine transporter deficiency.
Mutations in the SLC6A8 gene lead to CTD.
Although CTD patients have the necessary AGAT and GAMT enzymes for creatine production, they suffer from a creatine deficiency. This is because, due to a missing or dysfunctional creatine transporter at the cell walls, creatine cannot be made available to the cells for energy production. As a result, creatine is present in the bloodstream but cannot reach the brain and muscles.
CTD patients do not have elevated GAA levels like GAMT patients and generally do not require a special diet.
To date, there is no proven effective treatment for CTD. Visit our research page to learn more about our initiatives to develop a cure for CTD!
On the following pages, we will focus particularly on CTD, as it is the most common of all creatine deficiency syndromes.