September is Newborn Screening Awareness Month
Newborn Screening for GAMT, one of the 3 CCDS, is being pilot tested in the State of Utah to support a future RUSP positive approval.
GAMT is a treatable disorder of the Cerebral Creatine Deficiency Syndromes.1
CEREBRAL CREATINE DEFICIENCY SYNDROMES CCDS
CCDS are genetic diseases that appear in early childhood and often result in severe intellectual disability.1
There are three diseases that make up the Creatine Deficiencies: AGAT, GAMT, and CTD.
WHAT ARE THE SIGNS AND SYMPTOMS OF CCDS?
• Global developmental delay, or GDD: 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
• Intellectual disability, or ID: Marked by serious limitations in intellectual functioning and behaviors and skills needed to function in daily life. ID is a term applied to older children whose intelligence can be measured with an IQ test. It appears before age 18 years.2
• Speech/language development delay3
• Seizures: Muscle stiffening and/or jerking
• Behavior disorders: Autism and attention deficit and/or hyperactivity disorders3
• Movement disorders: Lack of coordination and delays in crawling, sitting and walking3,4
• Vomiting and Digestive Problems
• Failure to thrive
Early Diagnosis is Critical to Help Preserve Brain Function¹
If an infant or young child is missing early developmental milestones, a healthcare professional may order several tests. When a creatine deficiency is suspected, these tests may be used to confirm (or not) the diagnosis:
- Urine and blood tests- measuring creatine and its metabolites5
- An imaging procedure called magnetic resonance spectroscopy (MRS)
- Genetic testing (ex. Whole Exome Sequencing – WES, NextGen panel tests targeting Epilepsy/Seizures, Autism Spectrum Disorders – ASD, and/or Intellectual Disability – ID)
AGAT and GAMT deficiencies are treatable conditions. Supplementary creatine, supplementary ornithine (an important amino acid), and a protein-restricted diet are often prescribed.
Healthcare professionals who specialize in the diagnosis and/or management of CCDS may include the following:
- Metabolic Geneticists
- Pediatric Neurologists
- Genetic Counselors
- Developmental-Behavioral Pediatricians
Connecting with others who understand and can help with patient/caregiver support for Creatine Deficiencies is important. Here are some of the organizations that could help.
(links are displayed in yellow)
Association for Creatine Deficiencies (ACD)
An international English speaking patient organization focused on the 3 Cerebral Creatine Deficiencies Syndromes
An international French/English speaking patient organization focused on X-linked intellectual disability disorders.
If you are a member of a Creatine Deficiencies patient organization and would like to be listed here, please contact us.
- Treatable inborn errors of metabolism causing intellectual disability: A systematic literature review
Clara D M van Karnebeek, Sylvia Stockler
Molecular Genetics and Metabolism 2012 Mar;105(3):368–81,
- AAP Definitions of ID and GDD accessed from:
Moeschler et al. Comprehensive Evaluation of the Child with Intellectual Disability or Global Developmental Delays. PediatricsSeptember 2014 http://pediatrics.aappublications.org/content/134/3/e903
- 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 September 12, 2018 https://www.ncbi.nlm.nih.gov/books/NBK3794/.
- 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.
- Sharer JD et al ACMG Standards and Guidelines |Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics Genetics in MedicineVol19, 256–263 (2017) https://www.nature.com/articles/gim2016203