CDD: Creatine Deficiency Syndromes

The creatine deficiency disorders (CDDs), inborn errors of creatine metabolism and transport, comprise three disorders:

1. Guanidinoacetate methyltransferase (GAMT) deficiency
2. L-arginine:glycine amidinotransferase (AGAT) deficiency
3. Creatine transporter (CRTR) deficiency

CDD

Male

Developmental delay and cognitive dysfunction or intellectual disability and speech-language disorder are common to all three CDDs.

• Onset of clinical manifestations of GAMT deficiency (reported in ~130 individuals) is between ages three months and two years; in addition to developmental delays, the majority of individuals have epilepsy and develop a behavior disorder (e.g., hyperactivity, autism, or self-injurious behavior), and about 30% have movement disorder.
• AGAT deficiency has been reported in 16 individuals; none have had epilepsy or movement disorders.
• Clinical findings of CRTR deficiency in affected males (reported in ~130 individuals) in addition to developmental delays include epilepsy (variable seizure types and may be intractable) and behavior disorders (e.g., attention deficit and/or hyperactivity, autistic features, impulsivity, social anxiety), hypotonia, and (less commonly) a movement disorder. Poor weight gain with constipation and prolonged QTc on EKG have been reported. While mild-to-moderate intellectual disability is commonly observed up to age four years, the majority of adult males with CRTR deficiency have been reported to have severe intellectual disability. Females heterozygous for CRTR deficiency are typically either asymptomatic or have mild intellectual disability, although a more severe phenotype resembling the male phenotype has been reported.

Yes

• Creatine Deficiency Disorders – National Institutes of Health

Connecting with others impacted by a rare disease allows for vital information to be shared about day-to-day life, prevents isolation, and gives hope. Please contact MitoAction for peer support opportunities at 888-MITO-411 or email mito411@mitoaction.org.

Other resources we recommend are:

• New Patient Kit for Mitochondrial Conditions
• Planning for Emergencies
• Monthly Expert Series
• Energy in Action Podcast