Keeping Glucose Transporter Type 1 Deficiency Syndrome in Mind: A Late Diagnosis and Unusual Neuroimage Findings

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Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1‐DS) is caused by impaired glucose transport into the brain and may associate with developmental delay, refractory early‐onset epilepsy, and movement disorders such as paroxysmal exercise‐induced dyskinesia (PEID).1, 2 In clinical practice, the diagnosis is based on low cerebrospinal fluid (CSF) glucose supported by low CSF lactate and/or detection of a pathogenic variant in the SLC2A1 gene. Quantification of GLUT1 in red blood cells is useful in ambiguous cases.3 Cerebral palsy (CP) is a common misdiagnosis, and, although unusual, GLUT1‐DS may be diagnosed in adulthood.1, 2

Case Report

A 52‐year‐old woman with previous diagnosis of CP and developmental delay, early‐onset epilepsy (generalized tonic‐clonic seizures and complex partial seizures), and episodic migraine without aura was referred to our Movement Disorders Clinic because of episodes of abnormal gait. Since childhood, she presented paroxysms of painful and disabling dystonic gait that were triggered by 10‐ to 20‐minute walks, with a frequency of four to five episodes per month. Dystonic position of the legs was mainly in adduction, flexion, and equinovarus. Symmetry, intensity, and latency were variable. These episodes improved after a few minutes of rest. They were unrelated with fasting or postpandrial state and unresponsive to levodopa (Video 1).

Head circumference was normal. EEG recorded during an episode of dystonia was normal. Cranial MRI (Fig. 1) and CT scan (Fig. 2) findings were consistent with bilateral putaminal iron deposition. A lumbar puncture showed hypoglycorrhachia (34 mg/dL) with a blood glucose level of 90 mg/dL and a CSF/blood glucose ratio of 0.37. Heterocygous pathogenic p.Arg126Cys mutation in SLC2A1 gene was disclosed.

Figure 1.

(A) Axial T2wTSE imaging at the level of the basal ganglia shows bilateral and symmetrical low signal in both pallidal and putaminal nuclei. (B) Axial GRE T2* weighted imaging at the same level shows exacerbated lower signal in both putaminal nuclei.

Figure 2.

Axial noncontrast CT scan at the same level than Figure 1 is normal, with absent calcium deposits in the basal ganglia.

After 6 months on strict ketogenic diet (KD), no further disabling episodes of PEID occurred, and migraine and seizures were controlled. Moreover, symptoms recurred transiently after a short period of incomplete adherence to KD.

Discussion

Most SLC2A1 mutations are de novo. No phenotype‐genotype correlations have been clearly established, although some types of mutations have been related to specific clinical manifestations.2 Patients who carried the mutation of our patient (pArg126Cys) had been previously reported3, 4, 5 and presented symptoms that included intellectual impairment, different types of seizures, spastic paraplegia, paroxysmal choreoathetosis, PEID, gait ataxia, dysarthria, and microcephaly with a variable age at diagnosis.4, 5, 6

Neuroimaging findings are usually noncontributory.2 To our knowledge, this is the first case of GLUT1‐DS with putaminal iron deposition. Although the present findings could be incidental, further reports could clarify the pathophysiological relevance of putaminal iron deposition in GLUT1‐DS.

The clinical spectrum of the disease is wide, and, as this case report illustrates, the delay on diagnosis is sometimes considerable. In patients with a chronic neurological disorder, paroxysmal manifestations such as PEID are an important clue to the diagnosis of GLUT1‐DS. Recognition of this syndrome is of critical importance given that treatment with KD may improve seizure control and movement disorders. Although degree of response clearly depends on the delay of diagnosis and severity of the manifestations,2 we have shown that this treatment could be worth trying in adult patients with long‐lasting disease when motor manifestations are disabling.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

V.R.‐C.: 1A, 1B, 1C, 3A

A.A.‐C.: 1A, 1B, 1C, 3A, 3B

R.T.: 3B

J.S.M.‐S.‐M.: 3B

Disclosures

Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors confirm that the approval of an institutional review board was not required for this work. Oral and written informed consent was obtained from the patient.

Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.

Financial Disclosures for previous 12 months: The authors declare that there are no disclosures to report.

Supporting information

Video 1. Segment 1 and segment 2: usual walking and running pattern that shows left lower limb dystonia and dystonic posturing of right upper limb, particularly on running and after running. Segment 3: After 15 minutes‐walk exercise, the patient developed an episode of dystonic gait with worsening of the left lower limb dystonia compatible with PEID.