Rare Hematology News

Disease Profile

X-linked creatine deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E72.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

rnn-xlinkedrecessive.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

notapplicable.svg

Other names (AKA)

X-linked creatine transporter deficiency; X-linked creatine deficiency syndrome; Creatine deficiency, X-linked

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

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]

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]

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.

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

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.

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

      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

      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

        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.

            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.

            Rare Hematology News