A rare disease a day: Glucose Transporter Type I Deficiency Syndrome

In honor of rare disease day this week, I am raising awareness of some of the rare diseases as brief posts. Following on from past installments of “A rare disease a day” Hunter syndrome, Gaucher disease, Tay-Sachs, Morquio syndrome, Fabry disease, Sanfilippo syndrome, Krabbe Disease, Niemann-Pick Disease, Batten disease , Hurler Syndrome, Charcot-Marie-Tooth, Fibromuscular dysplasia, Huntington’s disease,  Giant Axonal Neuropathy (GAN). Neuroendocrine tumor, Amyloidosis, Lowe syndrome , Rett Syndrome and now its the turn of Glucose Transporter Type I Deficiency Syndrome .


Glucose Transporter Type I Deficiency Syndrome (Glut1 Deficiency, Glut1 DS, G1D, or De Vivo Disease) is a genetic disorder that impairs brain metabolism. Patients with Glut1 Deficiency have insufficient cellular energy to permit normal brain growth and function.The disease causes infantile seizures refractory to anticonvulsive drugs, developmental delay, acquired microcephaly and neurologic manifestations including spasticity, hypotonia, and ataxia.  Developmental delays are often global and include receptive and expressive language dysfunction. The disease is diagnosed with CSF glucose value, (<2.2 mmol/L), or lowered CSF/plasma glucose ratio (<0.4), erythrocyte 3-O-methyl-d-glucose uptake assay.


The GLUT1 protein is used to transport glucose across the blood–brain barrier or the boundary separating tiny blood vessels from brain tissue. Mutations in the SLCA21 gene can cause the glucose transporter to decrease in function or stop completely. As a result there is less glucose available. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT1 also behaves as an enzyme and a receptor used by the HTLV virus to gain entry into target cells.


There is no cure for Glut1 deficiency syndrome. The disorder is commonly treated with the ketogenic diet (modified Atkins diet), which may prevent seizure activity in many individuals with Glut1 deficiency syndrome. There is however clinical trials ongoing which include the nutritional supplemement  triheptanoin (or C7) from Ultragenyx. A phase II open label trial has begun and there are several listed at clinical trials.gov. This molecule appears promising as an antiepileptic in mouse and suggested heptanoate metabolism is important.


Patient and foundation group links can be found on the rare connect site. A registry for the disease was recently started also.



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