Association between coenzyme Q10 and glucose transporter (GLUT1) deficiency

BMC Pediatrics

Rafael Artuch²  Plácido Navas⁴  Mercedes Pineda²  Cecilia Jimenez-Mallebrera²  Paz Briones³  Angela Gavilan⁴  Maria V Cascajo⁴  Maria A Aracil²  Esperanza Castejon²  Cristina Jou²  Maria A Rodríguez²  Carmina Espinos¹  Judith Armstrong²  Aida Ormazabal²  Raquel Montero²  Mar O’Callaghan²  Delia Yubero² 

[1]Insituto de Investigación Príncipe Felipe, CIBERER, Valencia, Spain

[2]Clinical Biochemistry, Pediatric Neurology, Histopathology, Gastroenterology-Nutrition and Neuromuscular Unit Departments. Hospital Sant Joan de Déu and Centre For research in rare diseases (CIBERER), Instituto de Salud Carlos III, Passeig Sant Joan de Déu, 2, Esplugues, 08950, Barcelona, Spain

[3]Instituto de Bioquimica Clínica, Hospital Clinic i provincial, CIBERER, Barcelona, Spain

[4]Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC-JA and CIBERER, Sevilla, Spain

关键词: Ketogenic diet;    Ataxia;    Coenzyme Q10;    SLC2A1 gene;    Glucose transporter type I deficiency;   

Others  :  1113350
DOI  :  10.1186/s12887-014-0284-5

 received in 2014-07-04, accepted in 2014-10-21,  发布年份 2014

【 摘 要 】

Background

It has been demonstrated that glucose transporter (GLUT1) deficiency in a mouse model causes a diminished cerebral lipid synthesis. This deficient lipid biosynthesis could contribute to secondary CoQ deficiency. We report here, for the first time an association between GLUT1 and coenzyme Q₁₀ deficiency in a pediatric patient.

Case presentation

We report a 15 year-old girl with truncal ataxia, nystagmus, dysarthria and myoclonic epilepsy as the main clinical features. Blood lactate and alanine values were increased, and coenzyme Q₁₀ was deficient both in muscle and fibroblasts. Coenzyme Q₁₀ supplementation was initiated, improving ataxia and nystagmus. Since dysarthria and myoclonic epilepsy persisted, a lumbar puncture was performed at 12 years of age disclosing diminished cerebrospinal glucose concentrations. Diagnosis of GLUT1 deficiency was confirmed by the presence of a de novo heterozygous variant (c.18+2T>G) in the SLC2A1 gene. No mutations were found in coenzyme Q₁₀ biosynthesis related genes. A ketogenic diet was initiated with an excellent clinical outcome. Functional studies in fibroblasts supported the potential pathogenicity of coenzyme Q₁₀ deficiency in GLUT1 mutant cells when compared with controls.

Conclusion

Our results suggest that coenzyme Q₁₀ deficiency might be a new factor in the pathogenesis of G1D, although this deficiency needs to be confirmed in a larger group of G1D patients as well as in animal models. Although ketogenic diet seems to correct the clinical consequences of CoQ deficiency, adjuvant treatment with CoQ could be trialled in this condition if our findings are confirmed in further G1D patients.

【 授权许可】

   
2014 Yubero et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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