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X-linked creatine deficiency


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Other Names:
X-linked creatine transporter deficiency; X-linked creatine deficiency syndrome; Creatine deficiency, X-linked
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


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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


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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: 2/1/2021

Cause Cause


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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


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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


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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


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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


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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


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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 MedlinePlus Genetics.

Related Diseases Related Diseases


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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.

Organizations Organizations


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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


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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.

News & Events News & Events


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News

  • Rare Disease Day at NIH 2021
    March 1, 2021

GARD Answers GARD Answers


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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


  1. Mercimek-Mahmutoglu S, Salomons GS. Creatine Deficiency Syndromes. GeneReviews. Updated Dec. 10, 2015; https://www.ncbi.nlm.nih.gov/books/NBK3794.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
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