Creatine Transporter Deficiency Presenting as Autism Spectrum Disorder.

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 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.

• Authors: Yılmaz Yıldız, Rahşan Göçmen, Ahmet Yaramış, Turgay Coşkun, Göknur Haliloğlu
• Journal: Pediatrics (Pediatrics) Vol. 146 Issue 5 (11 2020) ISSN: 1098-4275 [Electronic] United States
• PMID: 33093139 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2020 by the American Academy of Pediatrics.

Chemical References

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

Topics

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