Clinical use
Measurement of creatine and its precursor, guanidinoacetate can be useful in the investigation and subsequent monitoring of suspected creatine biosynthetic and uptake disorders. For initial screening, both plasma and urine samples should be obtained. For monitoring of patients with a diagnosis of guanidinoacetate methyltransferase deficiency or arginine:glycine amidinotransferase deficiency only a plasma sample is required.
Background
Creatine is produced mainly by the kidneys and liver from guanidinoacetate (GAA) and is stored by tissues with high energy requirements, notably the brain and skeletal muscle. The phosphorylated form is used in the formation of ATP in these tissues. Three inherited disorders that inhibit creatine utilisation have been identified: guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency and x-linked creatine transporter defect (CRTR). GAMT catalyses the conversion of GAA to creatine, and AGAT catalyses the production of GAA from glycine, therefore deficiencies of these enzymes cause defects in creatine biosynthesis. CRTR causes a disruption in creatine uptake by tissues. These conditions result in creatine deficiency within tissues that have high energy requirements, producing clinical manifestations such as intellectual disability, behavioural issues, autism, epilepsy and delayed speech. Muscular hypotrophy and myopathy may also be a feature. These conditions produce different patterns of results: AGAT has reduction in both creatine and GAA, while AGAT has high low creatine and high GAA. Males with CRTR have increased urinary creatine excretion.
Reference ranges
| Test | Age range | Reference range |
|---|---|---|
| Plasma creatine | ≤10 years 10 years | 41 – 115µmol/L 8 – 89 µmol/L |
| Plasma GAA | ≤10 years 10 years | 0.55 – 2.36 µmol/L 0.85 – 3.31 µmol/L |
| Urine Creatine:creat ratio | ≤5 years >5 and ≤12 years 12 years | 6 – 1303 µmol/mmol creatinine 9 – 617 µmol/mmol creatinine 5 – 58 µmol/mmol creatinine |
| Urine GAA:creat ratio | ≤5 years >5 and ≤12 years 12 years | 19 – 210 µmol/mmol creatinine 10 – 125 µmol/mmol creatinine 10 – 69 µmol/mmol creatinine |
Patient preparation
None required
Specimen requirements
- Plasma: Lithium heparin (dark green top) tube
- Urine: random, plain universal container
Limitations/Restrictions
None
Turnaround time
30 days
Analysing laboratory
Biochemical Genetics, Specialist Laboratory Medicine, Block 46, St James Hospital, Leeds, Beckett Street, LS9 7TF