Case Report: X-Linked Creatine Transporter Deficiency in Two Saudi Brothers with Autism.
Order a urine creatine test when autism comes with floppy tone, motor delay, or seizures—rare but treatable defects hide there.
01Research in Context
What this study did
Two Saudi brothers with autism came to a genetics clinic. Both had early birth, floppy tone, late walking, and seizures.
Doctors ran a full metabolic panel. A urine test showed almost no creatine. Gene testing confirmed creatine transporter deficiency.
What they found
The boys carried a rare X-linked SLC6A8 defect. This blocks creatine from entering the brain.
Once the defect was found, the family could try creatine supplements and plan for future trials.
How this fits with other research
Wang et al. (2010) tested urine creatine in the kids with autism and 50 controls. They saw no group difference and told clinicians not to screen. The new case seems to clash, but it doesn’t. Lv looked at average kids; Mohammed caught the rare outliers with clear red flags.
Zwaigenbaum et al. (2003) found muscular dystrophy in two toddlers sent for autism checks. Both papers show the same lesson: when autism sits beside motor delay, seizures, or floppy tone, dig deeper.
Lussu et al. (2017) used broad urine metabolomics in autism and found oxidative stress markers. Their wide-net approach supports adding targeted creatine tests when clinical clues appear.
Why it matters
You will not screen every child with autism for creatine defects. You will screen the ones who were preterm, hypotonic, late to walk, or have seizures. One extra urine test can reveal a treatable inborn error and give the family a precise answer.
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02At a glance
03Original abstract
Autism spectrum disorder (ASD) is the most common disability-causing neurodevelopmental disorder in childhood. Although inborn errors of metabolism (IEM) are rare causes of ASD, they are significant for several reasons, including implications in genetic counseling and determination of prognosis. In this article, we present a 6-year-old boy who presented to us with ASD and was diagnosed with creatine transporter deficiency. Physical and neurologic examination of this patient had not previously raised suspicion of IEM, but twin pregnancy, prematurity, NICU stay due to necrotizing enterocolitis, transient infantile hypotonia, gross-motor delay, breath-holding spells, and a single febrile seizure complicated the history. MRI revealed mild T2-hyperintensity in posterior periventricular white matter. Further evaluation with magnetic resonance spectroscopy, which showed a decreased creatine peak, led to diagnostic investigations for disorders of creatine metabolism, revealing increased urinary creatine:creatinine ratio and a de novo, novel hemizygous frameshift variant in <i>SLC6A8</i> Clinicians are advised to maintain a high index of suspicion for IEM and to evaluate patients with ASD for syndromic features. Although current guidelines from relevant organizations differ in their recommendations regarding the necessity and the extent of metabolic screening in ASD, there is a growing trend toward screening for treatable IEM. In this case report, we present challenges and pitfalls in the diagnostic journey for creatine transporter deficiency and underline the significance of a thorough history and physical examination in the evaluation of a child with ASD.
Journal of autism and developmental disorders, 2023 · doi:10.1542/peds.2019-3460