A 23-year-old woman presented to our hospital with involuntary movement attacks, which she had exhibited for about 20 years. The patient has an unremarkable family history, and her antenatal and perinatal histories and postnatal development were uneventful. At the age of 2, she underwent her first non-febrile generalized seizure. She was administered sodium valproate for 1 year. While another seizure occurred at the age of 12, the patient had since remained seizure-free. At the age of 3 years, involuntary movement attacks without impairment of consciousness began to occur after prolonged exercise or fasting. Attacks were characterized by intermittent dystonia of right unilateral limbs, manifesting as elbow joint, wrist joint, knee joint alternating flexion, twist, and adduction, especially the upper limb. Left limbs were involved occasionally. The involuntary movements lasted from 3 to 5 min. The episodes occurred only one or two times every month. She was diagnosed with dystonia, but no drugs were prescribed. The attacks often occurred before menstruation since her adolescence. At the age of 21 years, the pattern of attacks did not change, but it occurred more frequently than before, about once a week. The patient received a prescription for oxcarbazepine; while the drug helped to control the symptoms at first, it gradually became unhelpful. Four months before admission, the patient's manifestations became less associated with exercise or fasting, and the frequency increased to two to three times weekly. Oxcarbazepine was replaced with carbamazepine. Two months before admission, the symptom worsened after a trip to the seaside: the patient experienced continuous attacks, presenting as involuntary movements of the right upper and lower limbs, with affected limbs becoming painful. The degree of movement was similar to previous attacks; however, the episodes lasted from 3 to 30 min with intervals of 15-20 min; carbamazepine combined with Madopar could not relieve her PDs. Her head circumference was normal. Psychomotor development did not show any abnormalities according to her parents. The timeline of the patient's symptom is shown in Figure 1.
Neurological examination revealed positive bilateral Hoffman signs and decreased muscle tone. Cranial nerves, motor strength, and sensory examination were normal. Brain and spine magnetic resonance imaging, lung computed tomography, and laboratory blood exams (including the assessments of ceruloplasmin and erythrocyte sedimentation rates) were unremarkable.
Prolonged electroencephalogram monitoring showed sharp-slow and delta waves in the bilateral frontal area (Figure 2). Considering the worsening of her symptoms after her travels and a low fever of under 38.0 C, which had begun 4 days before admission to our hospital, we supposed that the worsened dyskinesia could be attributed to infectious factors. After written informed consent was obtained from the patient, lumbar puncture was performed, which showed a white blood cell (WBC) count of 20 x 106/L and a glucose concentration of 1.9 mmol/L (reference value: 2.3-4.1 mmol/L) in CSF; before the lumbar puncture, the patient's blood glucose concentration was 4.39 mmol/L. The CSF:blood glucose ratio was 0.43 (normal range: 0.62-0.68) [3]. These findings informed a speculative diagnosis of intracranial infection. However, antibody testing for M. tuberculosis and viruses in the blood and smear tests for M. tuberculosis and Cryptococcus in CSF showed negative results. A second lumbar puncture was performed 6 days later, showing a WBC of 2 x 106/L and a glucose concentration of 2.0 mmol/L in CSF. Tested the same morning, the patient's blood glucose concentration was 4.50 mmol/L; the ratio of CSF to blood glucose concentration was 0.44. Though the WBC in the CSF decreased to normal levels, the patient's symptoms did not abate fully. Her symptoms, medical history, and persistent reduced CSF:blood glucose ratios together suggested a neurometabolic disorder. We therefore subjected the patient and her parents to genetic analyses and identified a heterozygous point mutation (c.940G>A) in exon 7 of the SLC2A1 gene, which causes a substitution of amino acid 314 from glycine to serine (p.Gly314Ser). The mutation was not found in her parents. Ultimately, the genetic analysis informed a diagnosis of Glut1-DS. The patient began a ketogenic diet (KD), and the PDs disappeared within 3 months.