Cerebral creatine deficiency disorders - A clinical, genetic and follow up study from India.

Autor: Passi GR; Department of Pediatrics & Pediatric Neurology, Choithram Hospital & Research Centre, Indore, India., Pandey S; Department of Pediatrics & Pediatric Neurology, Santokba Durlabhji Memorial Hospital, Jaipur, India., Devi ARR; Department of Genetics and Pediatric Neurology, Rainbow Children's Hospital, Hyderabad, India., Konanki R; Department of Genetics and Pediatric Neurology, Rainbow Children's Hospital, Hyderabad, India., Jain AR; Department of Genetics and Pediatric Neurology, Rainbow Children's Hospital, Hyderabad, India., Bhatnagar S; Department of Radio Diagnosis, Sri Aurobindo Institute of Medical Sciences, Indore, India., Tripathi R; Department of Pediatrics & Pediatric Neurology, Choithram Hospital & Research Centre, Indore, India., Jain V; Department of Pediatrics & Pediatric Neurology, Santokba Durlabhji Memorial Hospital, Jaipur, India. Electronic address: vivek.jain@sdmh.in.
Jazyk: angličtina
Zdroj: Brain & development [Brain Dev] 2022 Apr; Vol. 44 (4), pp. 271-280. Date of Electronic Publication: 2021 Dec 30.
DOI: 10.1016/j.braindev.2021.12.004
Abstrakt: Introduction: Cerebral creatine deficiency syndromes (CCDS) are a group of potentially treatable neurometabolic disorders. The clinical, genetic profile and follow up outcome of Indian CCDS patients is presented.
Materials and Methods: This was a retrospective cohort of CCDS patients seen over six-years. Diagnosis was based either on low creatine peak on proton magnetic resonance spectroscopy (MRS) and/or genetic evaluation.
Results: Thirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. The mean (±SD) age at diagnosis was 7.2(±5.0) years. Clinical manifestations included intellectual disability (ID) with significant expressive speech delay in all. Most had significant behavior issues (8/13) and/or autism (8/13). All had history of convulsive seizures (11/13 had epilepsy; 2 patients only had febrile seizures) and 2/13 had movement disorder. Constipation was the commonest non-neurological manifestation (5/13 patients). Cranial MRI was normal in all CTD patients but showed globus pallidus hyperintensity in all four with GAMT deficiency. MRS performed in 11/13 patients, revealed abnormally low creatine peak. A causative genetic variant (novel mutation in nine) was identified in 12 patients. Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation.
Conclusion: Intellectual disability, disproportionate speech delay, autism, and epilepsy, were common in our CCDS patients. A normal structural neuroimaging with easily controlled febrile and/or afebrile seizures differentiated CTD from GAMT deficiency patients who had abnormal neuroimaging and often difficult to control epilepsy and movement disorder.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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