FAQ About Cerebral Creatine Deficiency Syndromes (CCDS)

1. How common is CTD? How common are the other creatine disorders?

Exactly how common CTD is remains unknown. Estimates suggest that CTD may be the cause of 1–2% of intellectual disability in males.1 (People with intellectual disability have difficulty thinking, learning, and developing the behaviors and skills needed to function in daily life.)2

The other creatine disorders—GAMT and AGAT deficiencies—are rarer.

2. What is the meaning of global developmental delay?

Global developmental delay, or GDD, refers to delay in meeting 2 or more developmental milestones, including body movements, large and small; speech and language; ability to think; social and personal skills; and daily life skills. GDD is a term applied to children under 5 years and typically predicts a future diagnosis of intellectual disability.2

3. Besides developmental delays, what are the other signs of CTD?

In addition to delays in speech, movement, and thinking ability, boys with CTD may experience seizures involving muscle stiffening and/or jerking; behavioral disorders such as autism and attention deficit and/or hyperactivity; lack of body coordination; digestive problems and vomiting; and an overall failure to thrive.3,4

4. Are CTD and other creatine disorders ever under-diagnosed?

Creatine disorders are under-diagnosed.

In other words, it is likely that CTD and other creatine disorders are diagnosed less often than they actually occur. Because these disorders are relatively rare and only recently discovered, some physicians may not know of their existence. Also, the symptoms of the creatine disorders can be observed as those of other disorders and may lead to diagnoses of autism, epilepsy, and cerebral palsy.

Here is a family's story that shares the travails about being under-diagnosed and then finally getting the CTD diagnosis.

http://abcnews.go.com/Health/mothers-intuition-leads-rare-diagnosis-son/story?id=27510756

5. What should I do if I think my child might have a creatine disorder?

If your child is missing developmental milestones, consult a healthcare professional who has been trained in creatine disorders and can arrange for appropriate tests: a metabolic geneticist, pediatric neurologist, genetic counselor, or developmental–behavioral pediatrician.

6. Is there a cure for CTD?

As of today, there is no cure for CTD. There are no highly effective treatments/therapies for CTD.

7. Do all children with CTD go on to develop intellectual disability?

All boys with CTD do and girls with CTD may or may not develop intellectual disability.

8. Can early diagnosis of creatine disorders prevent development of severe symptoms later on?

GAMT deficiency and AGAT deficiency are treatable by oral supplementation with creatine monohydrate. So an early diagnosis and appropriate treatment can reduce the severity of—and may even prevent—symptoms developing later on.3

Early CTD diagnosis cannot prevent development of intellectual disability and other symptoms. But an early diagnosis is helpful to start therapies for symptom relief.3

9. Is there a way to know for certain if my child has CTD?

When a creatine disorder is suspected, a healthcare professional will typically order specific urine and blood tests, an imaging procedure called magnetic resonance spectroscopy (MRS) and genetic testing of the SLC6A8 gene.

10. My son has a diagnosis of CTD confirmed by genetic testing. How can I help him?

Depending on the type and severity of your son’s symptoms, he may benefit from therapies aimed at improving his physical coordination, fine motor skills, speech and language skills, and behavior. If your son experiences seizures, drugs used to control epilepsy may help to manage them.3

You and your son may also want to participate in an observational study under way now. Your son may also be eligible to participate in clinical trials of CTD medications in the future.

11. Can my son participate in the observational study even if we don’t live near a test site?

Yes. Study locations are yet to be decided and travel stipends will be available for study participants who need them. If you think your son might qualify to participate, sign up to find out if he does. If he qualifies, travel to and from the nearest test site can be arranged.

12. If my son has CTD, should my spouse and I undergo genetic testing, too? And if he has siblings?

X-linked disorders such as CTD may only be passed on to children by the mother, so fathers do not need to be tested. Mothers are typically advised to undergo genetic testing, especially if they would like to have more children3. Siblings should also be tested for the disorder when there are positive genetic testing results for a family member.

References:

1. U.S. National Library of Medicine. X-linked creatine deficiency. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency. Published December 1, 2016.

2. AAP Definitions of ID and GDD accessed from:
Moeschler et al. Comprehensive Evaluation of the Child with Intellectual Disability or Global Developmental Delays. Pediatrics September 2014 http://pediatrics.aappublications.org/content/134/3/e903

3. Mercimek-Mahmutoglu S, Salomons GS. Creatine Deficiency Syndromes. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2015 Published January 15, 2009. Updated December 10, 2015. Accessed December 19, 2016 https://www.ncbi.nlm.nih.gov/books/NBK3794/.

4. Miller JS et al. Red Flags for Creatine Transporter Deficiency, and Potential Outcome Variables for the Severely Impaired. Poster first presented at Society for Developmental Behavioral Pediatrics (SDBP) 2016 Annual Meeting Savannah,GA September 2016.