Association for Creatine Deficiencies

Cycle 1

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Three Cerebral Creatine Deficiency Syndromes (CCDS)—Creatine Transporter Deficiency (CTD), Guanidinoacetate Methyltransferase (GAMT) Deficiency, L-Arginine:Glycine Amidinotransferase (AGAT) Deficiency—are inborn errors of metabolism, which interrupt the formation or transportation of creatine. Speech delay is one of the most pronounced symptoms of all three CCDS.

Last updated 04/30/2026

Clinical

Disease Class

Cerebral Creatine Deficiency Syndromes

Genetic diseases

Inherited metabolic disorder

Neurological diseases

Body Systems

Digestive

Metabolic

Muscular / Skeletal

Nervous / Sensory

Organs

Brain

Heart

Liver

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

GAMT

GATM

SLC6A8

Contributory Genes

None specified / unknown

Type of Inheritance

Autosomal recessive

X-linked recessive

Newborn Screening

Yes, for some genes

Disease Mechanism(s)

Creatine synthesis/transport defect

Enzyme deficiency

Transport defect

Age of Onset

Early childhood (age 1+-5)

Infancy (age 0-1)

Average Age at Diagnosis

Early childhood (age 1+-5)

Life Expectancy

Adulthood (age 18-64)

Affected Sex(es)

Female

Male

National Prevalence

1001-10000

Global Prevalence

10000+

National Incidence

Less than 10

Global Incidence

Less than 10

Symptoms / Phenotypes

autism

autistic behavior

cardiac abnormalities

failure to thrive

hyperactivity

hypotonia

intellectual delay / global developmental delay

movement disorders / ataxia / tremor

seizures / epilepsy

speech delay

vomiting / nausea

Biomarkers

Diagnostic

· abnormalities of urine and plasma GAA, Creatine, and Creatinine, and lack of MRS creatine peak

Monitoring

· plasma GAA and creatine for GAMT

Existing Therapies

Alternative treatments (eg. nutritional supplements)

Off-Label Drug Use

Therapies in Development

Gene therapy

· 3 total: 4-CTD, 2-GAMT, and 1-AGAT

Other (please specify)

· 2 RBCEV GAMT mRNA, GAMT Enzyme Replacement Therapy

Repurposed drug

· 1 Phenylbutyrate

Small molecule therapy (novel small molecule drugs)

· 3 undisclosed

Therapeutic Development Stages

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Data sharing

Focus group participation or coordination

Funding

Meetings with regulators (e.g., FDA listening sessions, PFDD meetings)

Outcome measures development

Recruitment and outreach to patients

Results dissemination (including publications)

Study material design and/or review (not protocol) — includes patient-facing materials such as informed consent

Study protocol design and/or review (includes selection of outcome measures)

Travel coordination

Organizational & Research

Cell Lines

Fibroblasts

iPSCs

LCLs

Cell Lines, Institution

Coriell Institute

Cell Lines, Involvement

Consulted

Cell Lines, share

All our cell lines are freely available

Disease Model

Mouse

Organoids

Rat

Disease Model, Involvement

Consulted

Funded

Disease Model, share

Some of our disease models are freely available

Organizational Challenges

None

Clinical Trial Role

Meeting with regulators

Outcome measures, development

Recruitment and outreach, patients

Study protocol design, review

Clinical Trial Types

Phase 1

Biobank, Institution

Coriell Institute

Biobank, Involvement

Consulted

Center of Excellence, Institution

University of Utah

Registry

Yes, we have a registry that we created

Data Collected, Registry

Clinical data

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Patients

Platform, Registry

IAMRARE

Natural History Study

Yes, we have a natural history study that we created

Data Collected, Natural History Study

Clinical endpoints (outcomes)

Genetic data

Medication usage

Patient-reported data

Retrospective data

Platform, Natural History Study

IAMRARE

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

Yes

ICD Codes

Yes, we have an ICD-11 code specific to our exact disease

Diagnostic Guidelines

Yes, we have guidance available on our website

Yes, we have accredited guidelines

Science Advisory Board Policies

No policies

Research Network Policies

Has CRN and willing to share policies

Patient Priority Survey

Yes

Patient Priority Survey, share

Yes, will share

Research Roadmap

Yes we have a Research Roadmap, and will share policies

Europe

Middle East

Oceania

Europe

None