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.
Arctic reindeer exhibit marked seasonal changes in fat deposition and mobilization. At intervals throughout the year, therefore, we have measured feed intake of both Svalbard (SR) and Norwegian reindeer (NR) together with the seasonal changes in size, lipogenic and lipolytic capacity of isolated adipocytes from both sub-species. Feed intake of both NR and SR was maximal in August, but declined thereafter, reaching minimum values in January (NR) and March (SR), 55 and 69% below the August value, respectively. NR and SR adipocyte volume changed in parallel and were reduced to the same extent (69%) from their maximum in August to their minimum in May. Adipocyte lipogenic capacity, measured as acetate incorporation into cellular lipid at saturated acetate concentrations, was lowest in January (NR adipocytes) and March (SR adipocytes), 92 and 90%, respectively, below the maximum values, which were obtained in August. Lipolytic capacity, measured as maximum adrenaline-stimulated glycerol release, was high in SR adipocytes from March through to October and in NR adipocytes from July through to January. Minimum lipolytic capacity, on the other hand, was found in January (SR adipocytes) and March (NR adipocytes). The present findings may be explained by alterations in lipogenic enzyme activity and in the lipolytic activation system.
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