Progressive Myoclonic Epilepsy'-like presentation of Cerebrotendinous Xanthomatosis in an Indian Family with A Novel C.646+1G>A Splice Site Mutation.

Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal-recessive inborn disorder of bile acid metabolism due to mutations in the CYP27A1 gene. It presents with a diverse range of neurological and non-neurological symptoms. We present a case of CTX with a progressive myoclonic epilepsy (PME) like phenotype and a family history of CTX. The proband had a generalized epilepsy with prominent myoclonus. He also had intellectual decline, ataxia, bipyramidal dysfunction and peripheral neuropathy. The younger sibling had a milder generalized epilepsy without myoclonus along with behavioral issues, ataxia, neuropathy, and prominent tendon xanthomas. Both the siblings had developmental cataracts. MRI Brain of both had dentate hyperintensities with cerebellar atrophy. The proband's EEG showed severe background slowing with multifocal interictal discharges. Targeted gene of analysis proband revealed a novel homozygous 5' splice site variation in intron 3 of the CYP27A1 gene. We present a novel phenotype and genotype of CTX presenting with a syndrome of myoclonic epilepsy. This is the first PME-like presentation of CTX to the best of our knowledge. CTX may present with a PME-like clinical phenotype and should be considered as a treatable cause within the differential diagnostic evluation of syndromic epilepsies involving an atypical familial myoclonic epilepsy.

Rare and Treatable Cause of Early-Onset Refractory Absence Seizures.

Glut-1 transporter deficiency syndrome (GLUT1-DS) is a rare disorder caused by the mutation in SLC2A1 gene, which results in impaired glucose transport into the brain. It has a broad spectrum of phenotypic presentation ranging from cognitive decline, microcephaly, and refractory seizures to complex movement disorder. Recognition of this disorder is necessary as it is refractory to antiepileptic drugs (AEDs) and responds significantly to ketogenic diet. We report a case of 7-year-old girl who presented with paroxysmal eye movements in infancy with early-onset absence epilepsy (EOAE), which worsened in early morning and on fasting and was found to be refractory to four AEDs. She had mild developmental delay and subtle ataxia. Cerebrospinal fluid showed hypoglycorrhachia, and molecular analysis identified deletion in exon 4 of SLC2A1 gene (p.leu169del), thus confirming GLUT1-DS. She had a near-complete seizure control on ketogenic diet. Thus, GLUT1-DS should be suspected in all cases of refractory generalized seizures specially EOAE, especially if it worsens on fasting, is associated with development delay, positive family history, or paroxysmal movement disorder.