A Treatable Cause of Intellectual Disability and Autism in a Young Child
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SCIENTIFIC LETTER
A Treatable Cause of Intellectual Disability and Autism in a Young Child Sangeetha Yoganathan 1 & Suvasini Sharma 2 & Mugil Varman 3 & Mukul Malhotra 1 & Mahalakshmi Chandran 1 & Gautham Arunachal 4 & Maya Thomas 1 Received: 2 July 2019 / Accepted: 29 January 2020 # Dr. K C Chaudhuri Foundation 2020
To the Editor: Cerebral creatine deficiency syndrome (CCDS), a potentially treatable neurometabolic disorder, manifests with developmental delay/intellectual disability and autistic features; and absent creatine peak on magnetic resonance spectroscopy (MRS). CCDS includes guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CRTR) deficiency. Creatine is transported across the brain and muscles by a sodium and chloride dependent creatine transporter encoded by the gene, SLC6A8 [1]. A five-year-old boy, first born of non-consanguineous parents was brought for the evaluation of expressive and receptive language delay. No antenatal or neonatal risk factors were identified. He had one brief episode of unprovoked generalised tonic seizure at 30 mo of age. His head circumference was 47 cm (< 3rd centile), height was 99 cm ( A in exon 8/intron 8 boundary [genomic coordinate chrX:152959473 G > A in GRCh37/hg19 build; Transcript ID for reference taken was ENST00000253122]. This variant has been predicted to be pathogenic. The child was treated with levetiracetam, creatine m o n o h y d r a t e ( 2 0 0 m g / k g / d ) , a rg i n i n e g r a n u l e s (300 mg/kg/d) and glycine (150 mg/kg/d) in divided doses, occupational therapy and speech therapy. Followup assessments revealed significant improvement in language, eye contact and social interaction. CRTR deficiency (OMIM 300352) is an X-linked disorder that manifests with varying degrees of developmental delay, autistic traits, receptive and expressive language dysfunction with or without seizures [1–3]. Other clinical features reported are oral dyspraxia, attention deficit, hyperactivity, aggressive behavior, spasticity, hypotonia, failure to thrive, feeding difficulties, disorders of coordination and movement disorders [2, 4]. MRI brain shows non-specific abnormalities such as cerebral atrophy, cerebellar atrophy, periventricular white matter hyperintensity, prominence of lateral ventricles, myelination delay, prominent subarachnoid spaces and thinning of corpus callosum while MRS consistently shows small or absent creatine peak [2, 4]. Elevated urinary creatine/creatinine ratio is a diagnostic biochemical marker for CRTR deficiency. Triple therapy with creatine monohydrate, glycine and arginine results in variable improvement [5]. We suggest that CRTR deficiency should be considered on the co-occurrence of the unexplained intellectual disability, autism, seizures and failure to thrive in a male child.
Indian J Pediatr
Compliance with Ethical Standards
3.
Conflict of Interest None. 4.
References 5. 1. 2.
Schulze A. Creatine deficiency syndromes. Mol Cell Biochem.
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