Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.
نویسندگان
چکیده
Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic diet.
منابع مشابه
Individualizing Treatment Approaches for Epileptic Patients with Glucose Transporter Type1 (GLUT-1) Deficiency
Monogenic and polygenic mutations are important contributors in patients suffering from epilepsy, including metabolic epilepsies which are inborn errors of metabolism with a good respond to specific dietetic treatments. Heterozygous variation in solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) and mutations of the GLUT1/SLC2A2 gene results in the failure of glucose tra...
متن کاملParoxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome
BACKGROUND Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. PHENOMENOLOGY SHOWN Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. EDUCATIONAL VALUE Proper identification of the paroxysmal events and early diagnos...
متن کاملCreatine Transporter Deficiency in Two Brothers with Autism Spectrum Disorder.
BACKGROUND Creatine transporter deficiency (CTD) is a treatable, X-linked, inborn error of metabolism. CASE CHARACTERISTICS Two brothers with autism spectrum disorder were diagnosed with CTD at the ages of 17 and 12 years. Both were found to have a previously reported hemizygous p.408delF (c.1216_1218delTTC) deletion mutation. OUTCOME Both patients were given creatine monohydrate, L-arginin...
متن کاملGLUT1 deficiency syndrome 2013: Current state of the art
Glucose transporter type 1 deficiency syndrome (GLUT1DS) is the result of impaired glucose transport into the brain. The "classic" GLUT1DS patient presents with infantile seizures (resistant to traditional seizure medications), developmental delay, acquired microcephaly, hypotonia, spasticity, and a complex movement disorder consisting of ataxia and dystonia. However, over the years, other clin...
متن کاملA Different SLC2A1 Gene Mutation in Glut 1 Deficiency Syndrome: c.734A>C
BACKGROUND Glucose transporter type 1 deficiency syndrome is the result of impaired glucose transport into the brain. Patients with glucose transporter type 1 syndrome may present with infantile seizures, developmental delay, acquired microcephaly, spasticity and ataxia. CASE REPORT Here, we report a rare case of glucose transporter type 1 deficiency syndrome caused by a different pathogenic ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Brain : a journal of neurology
دوره 133 Pt 3 شماره
صفحات -
تاریخ انتشار 2010