Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review
(1) Background: X-linked creatine transporter deficiency (CTD) (OMIM 300036) is a rare group of inherited metabolic disorders characterized by global developmental delay/intellectual disability (GDD/ID), seizures, autistic behavior, and movement disorders. Pathogenic variants in the <i>SLC6A8&...
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MDPI AG
2023-09-01
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| _version_ | 1797574539184439296 |
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| author | Jiaqing Li Sanqing Xu |
| author_facet | Jiaqing Li Sanqing Xu |
| author_sort | Jiaqing Li |
| collection | DOAJ |
| description | (1) Background: X-linked creatine transporter deficiency (CTD) (OMIM 300036) is a rare group of inherited metabolic disorders characterized by global developmental delay/intellectual disability (GDD/ID), seizures, autistic behavior, and movement disorders. Pathogenic variants in the <i>SLC6A8</i> gene, located at Xq28, are causative of the disease, leading to impaired creatine transport into the brain. Supplementation with creatine and its precursors, glycine and arginine, has been attempted, yet the treatment efficacy remains controversial. (2) Methods: Here we report a de novo <i>SLC6A8</i> variant in a boy aged 3 years 9 months presenting with GDD, autistic behavior, and epilepsy. Elevated urinary creatine/creatinine ratio and diminished creatine peak on brain MR spectroscopy suggested the diagnosis of CTD. Genetic sequencing revealed a de novo hemizygous frameshift variant (NM_005629: c.1136_1137del, p. Glu379ValfsTer85). Creatine supplementation therapy was initiated after definitive diagnosis. Electroencephalography and MR spectroscopy were monitored during follow-up in concurrence with neuropsychological evaluations. The clinical phenotype and treatment response of CTD were summarized by systematic view of the literature. (3) Results: In silico analysis showed this variant to be deleterious, probably interfering with substrate binding and conformational changes during creatine transport. Creatine supplementation therapy led to seizure cessation and modest cognitive improvement after half-year’s treatment. (4) Conclusions: This case highlights the importance of MR spectroscopy and metabolic screening in males with GDD/ID, allowing for early diagnosis and therapeutic intervention. Mechanistic understanding and case-per-se analysis are required to enable precision treatment for the patients. |
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| format | Article |
| id | doaj.art-d4ca7e8366944b1da061d5a17f33069c |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T21:23:55Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj.art-d4ca7e8366944b1da061d5a17f33069c2023-11-19T15:52:09ZengMDPI AGBrain Sciences2076-34252023-09-011310138210.3390/brainsci13101382Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature ReviewJiaqing Li0Sanqing Xu1Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China(1) Background: X-linked creatine transporter deficiency (CTD) (OMIM 300036) is a rare group of inherited metabolic disorders characterized by global developmental delay/intellectual disability (GDD/ID), seizures, autistic behavior, and movement disorders. Pathogenic variants in the <i>SLC6A8</i> gene, located at Xq28, are causative of the disease, leading to impaired creatine transport into the brain. Supplementation with creatine and its precursors, glycine and arginine, has been attempted, yet the treatment efficacy remains controversial. (2) Methods: Here we report a de novo <i>SLC6A8</i> variant in a boy aged 3 years 9 months presenting with GDD, autistic behavior, and epilepsy. Elevated urinary creatine/creatinine ratio and diminished creatine peak on brain MR spectroscopy suggested the diagnosis of CTD. Genetic sequencing revealed a de novo hemizygous frameshift variant (NM_005629: c.1136_1137del, p. Glu379ValfsTer85). Creatine supplementation therapy was initiated after definitive diagnosis. Electroencephalography and MR spectroscopy were monitored during follow-up in concurrence with neuropsychological evaluations. The clinical phenotype and treatment response of CTD were summarized by systematic view of the literature. (3) Results: In silico analysis showed this variant to be deleterious, probably interfering with substrate binding and conformational changes during creatine transport. Creatine supplementation therapy led to seizure cessation and modest cognitive improvement after half-year’s treatment. (4) Conclusions: This case highlights the importance of MR spectroscopy and metabolic screening in males with GDD/ID, allowing for early diagnosis and therapeutic intervention. Mechanistic understanding and case-per-se analysis are required to enable precision treatment for the patients.https://www.mdpi.com/2076-3425/13/10/1382creatine transporter deficiencydevelopmental delayMR spectroscopyepilepsy<i>SLC6A8</i> |
| spellingShingle | Jiaqing Li Sanqing Xu Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review Brain Sciences creatine transporter deficiency developmental delay MR spectroscopy epilepsy <i>SLC6A8</i> |
| title | Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review |
| title_full | Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review |
| title_fullStr | Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review |
| title_full_unstemmed | Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review |
| title_short | Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review |
| title_sort | diagnosis and treatment of x linked creatine transporter deficiency case report and literature review |
| topic | creatine transporter deficiency developmental delay MR spectroscopy epilepsy <i>SLC6A8</i> |
| url | https://www.mdpi.com/2076-3425/13/10/1382 |
| work_keys_str_mv | AT jiaqingli diagnosisandtreatmentofxlinkedcreatinetransporterdeficiencycasereportandliteraturereview AT sanqingxu diagnosisandtreatmentofxlinkedcreatinetransporterdeficiencycasereportandliteraturereview |