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Creatine transporter deficiency in two half-brothers
Orly Ardon1, Cristina Amat di San Filippo, Gajja S Salomons
1Division of Medical Genetics, ARUP Inst Clinical and Experimental Pathology, University of Utah, Salt Lake City, Utah.
American Journal of Medical Genetics. Part A
|July 6, 2010
Summary
X-linked creatine transporter deficiency, caused by SLC6A8 gene mutations, impairs creatine transport. Measuring creatine transport in fibroblasts confirms this rare neurological disorder in affected males.
Area of Science:
- Neuroscience and Genetics
- Biochemical and Metabolic Disorders
Background:
- X-linked creatine deficiency syndrome results from mutations in the SLC6A8 gene, which encodes the creatine transporter.
- This condition leads to impaired creatine uptake in the brain, causing significant neurodevelopmental challenges.
Observation:
- Two half-brothers presented with developmental delays, failure to thrive, and neurological symptoms including seizures.
- Brain imaging revealed white matter abnormalities, and MR spectroscopy showed reduced creatine levels.
- Biochemical tests indicated elevated urine creatine/creatinine ratios but normal plasma creatine and guanidinoacetate.
Findings:
- Human fibroblasts exhibit a single, saturable creatine transporter with specific kinetic properties (Km = 34.7 ± 2.5 μM).
- Fibroblasts from the affected individuals demonstrated a complete absence of creatine transport.
- Genetic analysis identified a novel frameshift deletion (c.974_975delCA, p.Thr325SerfsX139) in the SLC6A8 gene in the propositus.
Implications:
- Measurement of creatine transport activity in fibroblasts serves as a definitive diagnostic method for creatine transporter deficiency.
- Understanding the specific transporter function aids in diagnosing and potentially managing this rare X-linked disorder.
- The study highlights the crucial role of creatine transport in normal brain development and function.
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