Sporadic and familial glut1ds Italian patients: A wide clinical variability

Abstract

The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling.

A 23 years follow-up study identifies GLUT1 deficiency syndrome initially diagnosed as complicated hereditary spastic paraplegia

“…Furthermore, epileptic manifestations, gait disturbances and cognitive performances, remained quite stable in adulthood. This observation is in agreement with the previously reported milder phenotype in familial cases compared to sporadic forms (De Giorgis et al, 2015). Nevertheless, the long follow-up allowed us to evaluate several generations along many years: we observed an increase in severity and an earlier clinical onset in the affected members of the latest generations compared to the antecedent ones, suggesting an anticipation effect.…”

From splitting GLUT1 deficiency syndromes to overlapping phenotypes

“…These data corroborating previous results suggest that the degree of disruption of glucose transport into the brain is related with the type and the severity of GLUT1DS. Noteworthy, patients with the same mutation exhibit a heterogeneous range of type and severity of symptoms, even in a same family [De Giorgis et al, 2015]. For instance, patients with the same mutations in either Arg126 (substituted for cysteine or histidine) or Thr295Met, had clinical presentations with partial overlap but also significant differences M A N U S C R I P T 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 17 (Tables 4 and 5).…”

Atypical Manifestations in Glut1 Deficiency Syndrome

“…22 Few citations of paroxysmal kinesigenic dyskinesia and paroxysmal nonkinesigenic dyskinesia associated with GLUT1 deficiency syndrome were reported. 2,22,23 In paroxysmal kinesigenic dyskinesia, dyskinesias are precipitated by voluntary movements and it usually lasts less than 5 minutes. Typically, an attack is induced by a sudden voluntary movement, an example of which is getting up quickly to answer the doorbell or the telephone.…”

“…The movement disorder is known to appear in teenage years or in early adulthood (Figure 1) but nothing has yet been reported on the various types of paroxysmal movement disorders. 2,19,20 A possible explanation for the limited effects of the ketogenic diet in these kinds of movement disorders is the fundamental difference between glucose and ketones as metabolic fuels. Glucose passes through the glycolytic pathway whereas ketones are converted in the mitochondria directly to acetylCoA, so glycolytic intermediates are affected only by glucose, not ketones.…”