X-linked creatine deficiency

Title

Other Names:

Mental retardation , X-linked with seizures, short stature and midface hypoplasia; Mental retardation , X-linked, with creatine transport deficiency; X-linked creatine transporter deficiency; Mental retardation , X-linked with seizures, short stature and midface hypoplasia; Mental retardation , X-linked, with creatine transport deficiency; X-linked creatine transporter deficiency; X-linked creatine deficiency syndrome; Creatine deficiency, X-linked See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; Newborn Screening See More

Summary Summary

X-linked creatine deficiency primarily affects development of the brain and nervous system. Symptoms can begin at any age, but usually begin in early childhood. These symptoms can include mild to severe intellectual disability, delayed speech development, behavioral problems, and seizures. The intellectual disability may get worse over time. X-linked creatine deficiency is caused by a SLC6A8 gene that is not working correctly. It is inherited in an X-linked pattern. Diagnosis is based on screening tests, clinical exam, and genetic testing. Treatment is focused on managing the symptoms.^[1]^[2]^[3]^[4]

Last updated: 8/4/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with X-linked creatine deficiency. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:^[1]^[2]^[3]

Intellectual disability
Delayed speech and language development
Behavioral issues
Seizures
Low muscle tone (hypotonia)
Uncoordinated movement (ataxia)
Gastrointestinal symptoms

Symptoms usually begin in childhood, but sometimes occur much later. Some of the symptoms of X-linked creatine deficiency may get worse over time, especially intellectual disability.^[1]^[2]

Last updated: 8/5/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 57 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal circulating creatine concentration	Abnormality of creatine metabolism	0012113
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Global developmental delay		0001263
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Seizure		0001250
30%-79% of people have these symptoms
Aganglionic megacolon	Enlarged colon lacking nerve cells	0002251
Ataxia		0001251
Athetosis	Involuntary writhing movements in fingers, hands, toes, and feet	0002305
Autistic behavior		0000729
Cachexia	Wasting syndrome	0004326
Chorea		0002072
Constipation		0002019
Dystonia		0001332
Hyperactivity	More active than typical	0000752
Hypertonia		0001276
Ileus		0002595
Malar flattening	Zygomatic flattening	0000272
Muscular hypotonia	Low or weak muscle tone	0001252
Open mouth	Gaped jawed appearance Gaped mouthed appearance Slack jawed appearance [ more ]	0000194
Self-mutilation	Deliberate self-harm Self mutilation [ more ]	0000742
Short stature	Decreased body height Small stature [ more ]	0004322
5%-29% of people have these symptoms
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Mask-like facies	Expressionless face Lack of facial expression Mask-like facial appearance [ more ]	0000298
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Ptosis	Drooping upper eyelid	0000508
Redundant skin	Loose redundant skin Redundant skin folds Sagging, redundant skin [ more ]	0001582
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis	Laboratory abnormality Metabolism abnormality [ more ]	0001939
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Attention deficit hyperactivity disorder	Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ]	0007018
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Delayed myelination		0012448
Exotropia	Outward facing eye ball	0000577
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Feeding difficulties in infancy		0008872
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hypermetropia	Farsightedness Long-sightedness [ more ]	0000540
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Impaired social interactions	Impaired social interaction Poor social interactions [ more ]	0000735
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Long face	Elongation of face Increased height of face Increased length of face Vertical elongation of face Vertical enlargement of face Vertical overgrowth of face [ more ]	0000276
Mandibular prognathia	Big lower jaw Increased projection of lower jaw Increased size of lower jaw Large lower jaw Prominent chin Prominent lower jaw [ more ]	0000303
Midface retrusion	Decreased size of midface Midface deficiency Underdevelopment of midface [ more ]	0011800
Motor delay		0001270
Myopathic facies		0002058
Narrow face	Decreased breadth of face Decreased width of face [ more ]	0000275
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Pes cavus	High-arched foot	0001761
Poor hand-eye coordination		0007057
Reduced brain creatine level by MRS		0025051
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Stereotypy	Repetitive movements Repetitive or self-injurious behavior [ more ]	0000733
Tall stature	Increased body height	0000098
Underfolded superior helices		0008583
Vomiting	Throwing up	0002013
X-linked recessive inheritance		0001419

Showing of 57 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 9/1/2020

Cause Cause

X-linked creatine deficiency occurs when the SLC6A8 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[1]

Last updated: 8/5/2020

Inheritance Inheritance

X-linked creatine deficiency is inherited in an X-linked pattern.^[1]^[2] X-linked means that the gene for the condition is located on the X-chromosome, one of the sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene is enough to cause the condition. In females (who have two X chromosomes), an alteration needs to occur in both copies of the gene to cause the condition.

X-linked recessive conditions affect males much more often than females. Females, who have one altered gene, are called carriers. While, most female carriers have no signs or symptoms of the condition, in rare cases, female carriers may experience some mild signs or symptoms.

A female who carries one X-linked gene alteration has a 50% or 1 in 2 chance of having a son with the condition and a 50% chance of having a daughter who is also a carrier. A male with an X-linked recessive condition cannot pass on the disorder to his sons, but all of his daughters will be carriers.

Sometimes a male child is the first person in a family with the condition. In this case, the gene alteration may have been inherited from the mother, or the alteration may have occurred by chance for the first time in the child (de novo).

Last updated: 8/5/2020

Diagnosis Diagnosis

X-linked creatine deficiency is diagnosed based on the symptoms, clinical exam, and the results of genetic testing.^[1]^[5] Screening tests looking for levels of specific chemicals in the urine are often used prior to genetic testing.

Last updated: 8/5/2020

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Treatment Treatment

Treatment for X-linked creatine deficiency is focused on managing the symptoms.^[3]

Specialists involved in the care of someone with X-linked creatine may include:

Neurologist
Speech/language pathologist
Occupational therapy
Physical therapy

Last updated: 8/5/2020

Statistics Statistics

It is unclear how many people have X-linked creatine deficiency. It has been reported in over 150 patients.^[5] It may account for about 2% of males with intellectual disability.

Last updated: 8/5/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes other disorders of creatine deficiency syndrome like guanidinoacetate methyltransferase deficiency and L-arginine:glycine amidinotransferase deficiency (see these terms). In cases with partial cerebral creatine deficiency, argininosuccinic aciduria, citrullinemia type I, and gyrate atrophy of the choroid and retina (see these terms) should be considered. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnosis includes other disorders of creatine deficiency syndrome like guanidinoacetate methyltransferase deficiency and L-arginine:glycine amidinotransferase deficiency (see these terms). In cases with partial cerebral creatine deficiency, argininosuccinic aciduria, citrullinemia type I, and gyrate atrophy of the choroid and retina (see these terms) should be considered.

Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Association for Creatine Deficiencies
6965 El Camino Real
Suite 105-598
Carlsbad, CA 92009
E-mail: kim@creatineinfo.org
Website: http://creatineinfo.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on X-linked creatine deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked creatine deficiency. Click on the link to view a sample search on this topic.

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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Mercimek-Mahmutoglu S, Salomons GS. Creatine Deficiency Syndromes. GeneReviews. Updated Dec. 10, 2015; https://www.ncbi.nlm.nih.gov/books/NBK3794.
van de Kamp JM, Btsalel OT, Mercimek-Mahmutoglu S, et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013; 50(7):463-472. https://pubmed.ncbi.nlm.nih.gov/23644449.
Miller JS, Thomas RP, Bennett A, et al. Early Indicators of Creatine Transporter Deficiency. J Pediatr. 2019; 206:283-285. https://pubmed.ncbi.nlm.nih.gov/30579583.
van de Kamp JM, Mancini GM, Salomons GS. X-linked creatine transporter deficiency: clinical aspects and pathophysiology. J Inherit Metab Dis. 2014;37(5):715-733. 2014; 37(5):715-733. https://pubmed.ncbi.nlm.nih.gov/24789340.
Sharer JD, Bdamer O, Longo N, Tortorelli S, Wamelink MM, Young S. Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics. Genet Med. 2017; 19(2):256-263. https://pubmed.ncbi.nlm.nih.gov/28055022.