Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) Secondary to a Novel Variant in the ITPA Gene Successfully Treated with Dietary Therapy
Naomi Nazareth Becerra Aguiar1, Melissa Fernanda Chavez-Castillo2, Rosa Elizabeth Marquez-Palacios2
1Faculty of Medicine, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México., 2Neuropediatrics Department, Hospital Civil de Guadalajara “Fray Antonio Alcalde”. Guadalajara, Jalisco, México
Objective:
To report a case of Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) linked to a novel ITPA variant and explore the effectiveness of a Low Glycemic Index Diet (LGID) for seizure control.
Background:
EIMFS is a rare developmental and epileptic encephalopathy (DEE) with a prevalence of 0.11 per 100,000 children. It manifests in early infancy with drug-resistant focal seizures that migrate between hemispheres, causing significant developmental delay/regression. The condition is primarily genetic (KCNT1 accounts for 50% of cases). Prognosis remains poor, depending on the underlying cause.
ITPA-related DEE is associated with biallelic loss-of-function mutations in the ITPA gene, which encodes a key enzyme in purine metabolism This rare autosomal recessive disorder is characterized by microcephaly, neurodegeneration, cerebral atrophy, and white matter abnormalities in infants. Fewer than a dozen cases have been reported, with only one linked to EIMFS. While the ketogenic diet has a 62.5% success rate in KCNT1-related EIMFS, its effectiveness in ITPA-related EIMFS is still unknown.
Results:
A 2-year, 10-month-old female presented a 2-year history of multifocal clonic seizures resistant to multiple antiseizure medications. Physical exam revealed microcephaly, central hypotonia, and continuous choreiform upper limb movements. MRI showed cortical atrophy and white matter abnormalities, while EEG revealed a migrating ictal pattern (Figure 1). Genetic testing identified a novel homozygous ITPA variant (c.488+1G>A). Despite treatment with various antiseizure drugs, seizures persisted, leading to frequent hospitalizations. At age 2, LGID was introduced with good tolerance and adherence; seizures have mostly occurred during infections, and her development has improved notably.
Conclusions:
EIMFS is a rare form of DEE, with only one case linked to the ITPA gene; however, our patient's mutation is novel. Identifying the etiology is crucial for guiding treatment and prognosis. Although our patient responded well to LGID, further research is needed to confirm its efficacy in other EIMFS cases.
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