Creatine Transporter Deficiency Presenting as Autism Spectrum Disorder

Pediatrics. 2020 Nov;146(5):e20193460. doi: 10.1542/peds.2019-3460.


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 SLC6A8 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.

Publication types

  • Case Reports

MeSH terms

  • Autism Spectrum Disorder / diagnosis
  • Autism Spectrum Disorder / drug therapy
  • Autism Spectrum Disorder / genetics*
  • Brain / diagnostic imaging
  • Brain Diseases, Metabolic, Inborn / diagnosis
  • Brain Diseases, Metabolic, Inborn / drug therapy
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Child
  • Creatine / deficiency*
  • Creatine / genetics
  • Creatinine / metabolism
  • Diseases in Twins / diagnosis
  • Diseases in Twins / drug therapy
  • Diseases in Twins / genetics*
  • Frameshift Mutation*
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / drug therapy
  • Intellectual Disability / genetics
  • Male
  • Mental Retardation, X-Linked / diagnosis
  • Mental Retardation, X-Linked / drug therapy
  • Mental Retardation, X-Linked / genetics*
  • Nerve Tissue Proteins / genetics*
  • Plasma Membrane Neurotransmitter Transport Proteins / deficiency*
  • Plasma Membrane Neurotransmitter Transport Proteins / genetics
  • Proton Magnetic Resonance Spectroscopy


  • Nerve Tissue Proteins
  • Plasma Membrane Neurotransmitter Transport Proteins
  • SLC6A8 protein, human
  • Creatinine
  • Creatine

Supplementary concepts

  • Creatine deficiency, X-linked