Association between coenzyme Q10 and glucose transporter (GLUT1) deficiency.
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.


METHODS
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.


CONCLUSIONS
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.
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, 08950, Esplugues, Barcelona, Spain. dyubero@fsjd.org.
Delia
D
Yubero
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, 08950, Esplugues, Barcelona, Spain. mocallaghan@hsjdbcn.org.
Mar
M
O'Callaghan
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, 08950, Esplugues, Barcelona, Spain. rmontero@hsjdbcn.org.
Raquel
R
Montero
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, 08950, Esplugues, Barcelona, Spain. aormazabal@hsjdbcn.org.
Aida
A
Ormazabal
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, 08950, Esplugues, Barcelona, Spain. jarmstrong@hsjdbcn.org.
Judith
J
Armstrong
Insituto de Investigación Príncipe Felipe, CIBERER, Valencia, Spain. cespinos@cipf.es.
Carmina
C
Espinos
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, 08950, Esplugues, Barcelona, Spain. laboratori@hsjdbcn.org.
Maria A
MA
Rodríguez
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, 08950, Esplugues, Barcelona, Spain. cjou@hsjdbcn.org.
Cristina
C
Jou
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, 08950, Esplugues, Barcelona, Spain. ecastejon@hsjdbcn.org.
Esperanza
E
Castejon
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, 08950, Esplugues, Barcelona, Spain. aaracil@hsjdbcn.org.
Maria A
MA
Aracil
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC-JA and CIBERER, Sevilla, Spain. mvcascajo@upo.es.
Maria V
MV
Cascajo
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC-JA and CIBERER, Sevilla, Spain. agavnar@upo.es.
Angela
A
Gavilan
Instituto de Bioquimica Clínica, Hospital Clinic i provincial, CIBERER, Barcelona, Spain. pbriones@clinic.ub.es.
Paz
P
Briones
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, 08950, Esplugues, Barcelona, Spain. cjimenezm@fsjd.org.
Cecilia
C
Jimenez-Mallebrera
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, 08950, Esplugues, Barcelona, Spain. pineda@hsjbcn.org.
Mercedes
M
Pineda
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC-JA and CIBERER, Sevilla, Spain. pnavas@upo.es.
Plácido
P
Navas
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, 08950, Esplugues, Barcelona, Spain. rartuch@hsjdbcn.org.
Rafael
R
Artuch
D000293:Adolescent; D001259:Ataxia / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology*; D027682:Cation Transport Proteins; D055423:Diet, Ketogenic; D019587:Dietary Supplements; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology*; D018908:Muscle Weakness / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology*; D009154:Mutation; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000172:deficiency* / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
D027682:Cation Transport Proteins; D051272:Glucose Transporter Type 1; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D014815:Vitamins; D014451:Ubiquinone; C024989:coenzyme Q10