Symptomatic West Syndrome Secondary to Glucose Transporter-1(GLUT1) Deficiency with Complete Response to 4:1 Ketogenic Diet
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- Vykuntaraju, K.N., Bhat, S., Sanjay, K.S. et al. Indian J Pediatr (2014) 81: 934. doi:10.1007/s12098-013-1044-5
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Glucose transporter type 1 (GLUT-1) deficiency is a rare cause of preventable intellectual disability. Intellectual disability is due to refractory seizures in infancy and reduced supply of glucose to the brain. The authors report a third born male child of consanguineous parentage who presented with infantile spasms. Initially, he had refractory convulsions of focal, generalised, and myoclonic jerks, not responding to multiple anticonvulsants. He also had choreoathetoid movements. On examination he had microcephaly. MRI of brain was normal and EEG showing diffuse slowing. CSF glucose was low compared to blood glucose, with normal lactate and without any cells, hence diagnosed as Glucose transporter-1 deficiency and started on ketogenic diet. With ketogenic diet, child was seizure free, anticonvulsants decreased to 2 from 5, and improvements in development were noted.
KeywordsCerebrospinal fluid glucoseGLUT1 deficiency syndromeIndiaKetogenic diet
Glucose transporter-1 (GLUT1) deficiency syndrome is a rare autosomal dominant disorder . GLUT1 is expressed in the endothelial cells of erythrocytes and the blood–brain barrier. GLUT is responsible for glucose transport into the brain, deficiency of this leads to reduced transport of glucose in to the brain. De Vivo et al. first described GLUT1 deficiency syndrome in 1991 . The classical features of GLUT1 deficiency syndrome are drug resistant seizures in infancy, developmental delay and an acquired microcephaly in up to 50 % of cases. The authors report a child with refractory multiple types of seizures in addition to infantile spasms, not responding to antiepileptic drugs later diagnosed as GLUT1 deficiency.
A 12-mo-old male child presented with infantile spasms since 5 mo of age. He had convulsions since day 25 of life and developmental delay. He had multiple episodes of convulsions of different types including infantile spasms. He attained head control, acquired Palmar grasp, and social smile around 5 mo of age (Developmental age-3 mo). Later, when he developed refractory seizures with infantile spasms he had lost the attained milestones of head control and social smile.
He was a third born child to a consanguineously married couple with a family history of similar complaints in the two of the elder male siblings having multiple refractory convulsions and were treated with multiple anticonvulsants but without any response. Finally both expired due to status epilepticus around 5 y of age. First two siblings also had developmental delay.
This child was on multiple anticonvulsants and ACTH for infantile spasms without any significant improvement in frequency of convulsions. He also received pyridoxine, biotin, and folinic acid without any response.
On examination his weight and length were normal. He had microcephaly (head circumference- 40.2 cm) with no neurocutaneous markers. His tone was decreased with brisk reflexes. He had oral dyskinetic movements and choreo-athetosis of both upper limbs.
Glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS) is defined by hypoglycorrhachia with normoglycemia, acquired microcephaly, episodic movements, and epilepsy refractory to standard antiepileptic drugs. Classically, patients present with epilepsy in infancy, developmental delay, acquired microcephaly, cognitive impairment, and varying degrees of spasticity, ataxia and dystonia. However, the presentation and course are variable. Other phenotypes have also been identified . One phenotype is characterized by intellectual disability, dysarthria, intermittent ataxia and absence of clinical seizures . Another phenotype is characterized by paroxysmal episodes of involuntary head and eye movements, and by chronic choreo-athetosis and dystonia . Recently, a new phenotype characterized by paroxysmal exercise induced dyskinesias with or without epilepsy has been reported .
The seizure onset most often occurs in infancy at 8 mo, with most patients manifesting generalized tonic–clonic or absence seizures. This child and other two siblings who had expired -manifested from neonatal period. Birth history was uneventful with normal birth weight and Apgar score. The diagnosis of GLUT-1DS was suspected due to a reduced CSF glucose concentration (hypoglycorrhachia, <40 mg/dL) in the setting of normal blood sugar with a CSF/blood glucose ratio ≤0.19. In the index patient, seizures did not respond to several anticonvulsant medications and thus CSF study was performed when the patient was 11 mo old. The results were compatible with GLUT-1DS. Diagnostic criteria for GLUT1 deficiency include developmental encephalopathy with seizures and/or episodic movement disorders, with hypoglycorrhachia and normoglycemia, and acquired microcephaly . All the clinical features and diagnostic criteria were present in the index child, hence diagnosed as GLUT1 deficiency syndrome.
The index patient was started on a 4:1 ketogenic diet at 11 mo of age and maintained the ketogenic diet till now. The ketogenic diet is effective in alleviating clinical findings (i.e., seizure control and in improving alertness and movement disorder). Ketone bodies use different transport mechanism to cross the blood–brain barrier. These ketone bodies provide alternative fuel to brain for metabolism. There have been no patients identified in India. This is the first known Indian patient with GLUT-1DS as per authors’ knowledge. Only 2 cases of west syndrome with GLUT1 deficiency have been described in a series of 87 cases . GLUT-1DS as a seizure condition of infancy, should be considered in any case of non-acquired epilepsy or paroxysmal movements in patients younger than age 1 y.
When a child presents with refractory convulsions and infantile spasms not responding to anticonvulsant drugs, simple CSF analysis to look for hypoglycorrhachia helps in diagnosis of GLUT1 deficiency. Ketogenic diet has to be started in these children for control of seizures and to prevent morbidity and mortality.
Conflict of Interest
Role of Funding Source
British Biological Pharmaceuticals provided Ketokid to the patient for free of cost.