Diagnosis for Physicians

Important Note

This article addresses a health-related topic. It is not intended for self-diagnosis and does not replace a doctor's diagnosis. Please refer to our General and Medical Disclaimer.

Notable Symptoms

Are you caring for patients who suffer from a combination of the following symptoms? Then check if one of the three creatine deficiency syndromes is present! In cases of intellectual disabilities of unknown origin, it may be worth investigating for a creatine deficiency syndrome, especially when there is a family history along with severe speech acquisition deficits, extrapyramidal syndromes, behavioral disorders, and/or the absence of dysmorphisms (Cheillan et al 2005 (opens new window)).

Multistage Diagnostics for Confirmed Diagnosis

Below is the diagnostic decision flow according to Curt et al 2015 (opens new window) (step-by-step diagnostic description below).

Step 1: Determine Creatine and Metabolites Using Urine Sample

Suspicion of a creatine deficiency syndrome is initially investigated through the examination of GAA and creatine in urine and/or plasma. An elevated creatine-to-creatinine ratio suggests a creatine transporter defect.

The determination of the creatine-creatinine ratio is of significant diagnostic value, as non-corrected creatine values in urine from patients with SLC6A8 deficiency may appear normal. In female patients with a creatine transporter defect, normal creatine levels in urine have been reported during urine screening, making the determination of creatine levels potentially insufficient in diagnostic procedures (Valayannopoulos 2012 (opens new window)).

Cold Chain and Time Chain

Adhering to the cold and time chain from sample collection to laboratory analysis is essential to minimize the degradation of creatine to creatinine in the urine.

Step 2: Cerebral 1H Magnetic Resonance Spectroscopy

Step 2, as a replacement or complement, is a cerebral 1H magnetic resonance spectroscopy, which captures the creatine deficiency in the brain to visualize the presumed decrease in cerebral creatine/phosphocreatine peak intensity.

Step 3: Confirming the Suspected Diagnosis Through Genetic Testing

Biochemical investigations are then confirmed through genetic testing.