Case report: Clinical and magnetic resonance spectroscopy presentation of a female severely affected with X-linked creatine transporter deficiency

Morey, Katherine; Hallinan, Barbara; Cecil, Kim M.

doi:10.1016/j.radcr.2022.01.053

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…As already mentioned, the extensive review by van de Kamp and others of 101 affected males reported MRI alterations in only 53 out of 76 patients in whom MRI data were available (70%); it should therefore be concluded that in the remaining 23 cases (30%), the MRI results were normal. Even more clearly, Morey et al reported the unusual but instructive case of a heterozygous female patient who was affected by creatine transporter deficiency and displayed severe symptoms despite normal conventional MRI results [38]. It is then noteworthy that in our two cases, abnormal tractography findings were observed in the face of normal conventional MRI results (Figure 1).…”

Section: Discussionmentioning

confidence: 54%

Selective Alteration of the Left Arcuate Fasciculus in Two Patients Affected by Creatine Transporter Deficiency

Balestrino,

Adriano,

Alì

et al. 2024

Brain Sciences

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(1) Background: In hereditary creatine transporter deficiency (CTD), there is an absence of creatine in the brain and neurological symptoms are present, including severe language impairment. However, the pathological changes caused by creatine deficiency that generate neuropsychological symptoms have been poorly studied. (2) Aims: To investigate if the language impairment in CTD is underpinned by possible pathological changes. (3) Methods: We used MRI tractography to investigate the trophism of the left arcuate fasciculus, a white matter bundle connecting Wernicke’s and Broca’s language areas that is specifically relevant for language establishment and maintenance, in two patients (28 and 18 y.o.). (4) Results: The T1 and T2 MRI imaging results were unremarkable, but the left arcuate fasciculus showed a marked decrease in mean fractional anisotropy (FA) compared to healthy controls. In contrast, the FA values in the corticospinal tract were similar to those of healthy controls. Although white matter atrophy has been reported in CTD, this is the first report to show a selective abnormality of the language-relevant arcuate fasciculus, suggesting a possible region-specific impact of creatine deficiency.

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Section: Discussionmentioning

confidence: 54%

Selective Alteration of the Left Arcuate Fasciculus in Two Patients Affected by Creatine Transporter Deficiency

Balestrino,

Adriano,

Alì

et al. 2024

Brain Sciences

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“…Valayannopoulos et al (2011) reported reduced creatine levels for two patients with 50 and 40% reductions. Morey et al (2022) reported a 60% creatine level reduction for their patient. Nielsen et al (2023) reported significantly decreased creatine compared with a control dataset.…”

Section: Discussionmentioning

confidence: 95%

“…(2011) reported reduced creatine levels for two patients with 50 and 40% reductions. Morey et al . (2022) reported a 60% creatine level reduction for their patient.…”

Section: Discussionmentioning

confidence: 99%

Arginine, glycine, and creatine supplementation improves symptoms in a female with creatine transporter deficiency

Tauer,

Theile,

Owens

et al. 2024

Psychiatric Genetics

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X-linked creatine transporter deficiency is caused by hemizygous or heterozygous pathogenic variants in SLC6A8 that cause neuropsychiatric symptoms because of impaired uptake of creatine into tissues throughout the body. Small cohorts have suggested that supplementation of creatine, arginine, and glycine can stop disease progression in males, but only six cases of supplementation in females have been published. Here, we present a female with a de-novo pathogenic SLC6A8 variant who had ongoing weight loss, mild intellectual disability, and neuropsychiatric symptoms. Magnetic resonance spectroscopy of the brain showed reduced creatine on all acquired spectra. The patient was started on creatine-monohydrate, l-arginine, and l-glycine supplementation, and she had significant symptomatic improvement within the following 3 weeks. After 8 months of supplementation, magnetic resonance spectroscopy showed improved creatine concentrations with normalizing semiquantitative ratios with other brain metabolites. Current data supports clinicians trialing creatine, arginine, and glycine supplements for female patients with creatine transporter deficiency.

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“…Some illustrative examples of recent discoveries reported after Fernandez-Castillo et al conducted their systematic review include patients presenting with ADHD symptoms due to deficiency of L-2-hydroxyglutarate dehydrogenase ( L2HGDH ) ( 34 ), X-linked creatine transporter deficiency ( 35 ) and HUWE1 mutations ( 36 ). These examples show that severe progressive neurological conditions may masquerade as common ADHD and that clinicians need to be aware of this possibility.…”

Section: Comorbid Conditionsmentioning

confidence: 99%

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Haavik

2022

Front. Psychiatry

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ADHD is a common behavioral syndrome with a heritability of 70–80%. Genome wide sequencing and association studies indicate that ADHD risk variants are distributed across a wide range of allele frequencies and relative risks. Several common single nucleotide variants (SNPs) have been identified that increase the risk of ADHD with a few percent. Many of the reported risk genes and copy number variants are shared with other neuropsychiatric disorders. Moreover, ADHD often coexists with common or rare somatic diseases, including rare Mendelian neurometabolic diseases that can affect normal brain development and function. Some genetic/metabolic syndromes masquerading as common ADHD may lead to irreversible brain damage if not properly identified and treated during early childhood. As ADHD is such a heterogeneous condition in terms of severity, clinical features and most probably also underlying biology, it is crucial to offer individualized treatments. Recent progress in ADHD genetics is reviewed, prospects of using this information for targeted pharmacotherapy are discussed and critical knowledge gaps are identified. It is suggested that genome guided therapies could be introduced gradually, starting with rare ADHD syndromes with highly penetrant risk genes. Routine diagnostic application of whole exome or whole genome sequencing combined with metabolomic screening, and brain imaging may be needed in cases with suspected neurometabolic disorders. Identification and treatment of ADHD patients with defined neurometabolic aberrations could be a first step toward genome guided personalized treatment of ADHD. Possibly, screening for relevant biomarkers may gradually be implemented to guide treatment choices in larger patient groups.

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Case report: Clinical and magnetic resonance spectroscopy presentation of a female severely affected with X-linked creatine transporter deficiency

Cited by 5 publications

References 22 publications

Selective Alteration of the Left Arcuate Fasciculus in Two Patients Affected by Creatine Transporter Deficiency

Selective Alteration of the Left Arcuate Fasciculus in Two Patients Affected by Creatine Transporter Deficiency

Arginine, glycine, and creatine supplementation improves symptoms in a female with creatine transporter deficiency

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

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