Creatine Disorders Panel, S

Imported from GeneReviews

The creatine deficiency disorders (CDDs), inborn errors of creatine metabolism and transport, comprise three disorders: the creatine biosynthesis disorders guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency; and creatine transporter (CRTR) deficiency. 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.

Imported from Human Phenotype Ontology (HPO)

• Aggressive behavior
• Cerebellar ataxia
• Febrile seizure (within the age range of 3 months to 6 years)
• Hypertonia
• Hypotonia
• Rigidity
• Myoclonus
• Seizure
• Intellectual disability, severe
• Tremor
• Hyperreflexia
• Paraparesis
• Atonic seizure
• Decreased serum creatinine
• Delayed speech and language development
• Bilateral tonic-clonic seizure
• Global developmental delay
• Lower limb spasticity
• Developmental regression
• Severe global developmental delay
• Episodic vomiting
• Absent speech
• Infantile muscular hypotonia
• Progressive extrapyramidal movement disorder
• Intellectual disability
• Reduced brain creatine level by MRS
• Elevated circulating guanidinoacetic acid concentration
• Elevated brain guanidinoacetate level by MRS
• Decreased urinary creatine level
• Reduced tissue guanidinoacetate methyltransferase activity