Urine creatine metabolite panel as a screening test in neurodevelopmental disorders

Shalini Bahl,Lauren Macneil,Dawn Cordeiro,Saadet Mercimek-Andrews,Andreas Schulze

doi:10.1186/s13023-020-01617-z

Abstract

BackgroundCerebral creatine deficiency disorders (CCDD) are inherited metabolic disorders of creatine synthesis and transport. Urine creatine metabolite panel is helpful to identify these disorders.MethodsWe reviewed electronic patient charts for all patients that underwent urine creatine metabolite panel testing in the metabolic laboratory at our institution.ResultsThere were 498 tests conducted on 413 patients. Clinical, molecular genetics and neuroimaging features were available in 318 patients. Two new patients were diagnosed with creatine transporter deficiency: one female and one male, both had markedly elevated urine creatine. Urine creatine metabolite panel was also used as a monitoring test in our metabolic laboratory. Diagnostic yield of urine creatine metabolite panel was 0.67% (2/297). There were six known patients with creatine transporter deficiency. The prevalence of creatine transporter deficiency was 2.64% in our study in patients with neurodevelopmental disorders who underwent screening or monitoring of CCDS at our institution.ConclusionEven though the diagnostic yield of urine creatine metabolite panel is low, it can successfully detect CCDD patients, despite many neurodevelopmental disorders are not a result of CCDD. To the best of our knowledge, this study is the first Canadian study to report diagnostic yield of urine creatine metabolite panel for CCDD from a single center.

Highlights

Cerebral creatine deficiency disorders (CCDD) are inherited metabolic disorders of creatine biosynthesis and transport
As all three disorders impair creatine metabolism and transport, males and females with guanidinoacetate methyltransferase (GAMT) and arginine-glycine amidino transferase (AGAT) deficiencies and males with creatine transporter (CRTR) deficiency have absent creatine in brain tissue when measured by magnetic resonance spectroscopy (MRS)
Urine guanidinoacetate (p = 0.001856) and creatine (p = 0.03946) levels were significantly different between males and females for the age group 0–60 months, whereas in other age groups, there was no statistically significant difference between males and females (Table 1)

Summary

Introduction

Cerebral creatine deficiency disorders (CCDD) are inherited metabolic disorders of creatine biosynthesis and transport. The characteristic biochemical features of each CCDD is unique: elevated guanidinoacetate in body fluids in GAMT deficiency, low or low normal urine guanidinoacetate and low plasma guanidinoacetate in AGAT deficiency and elevated urine creatine in CRTR deficiency in males. Because of these abnormalities, a urine creatine metabolite panel that measures guanidinoacetate, creatine and creatinine can be used as a screening test for CCDD. Urine creatine metabolite panel is helpful to identify these disorders

Methods

Results

Conclusion