Infantile Alexander Disease Presenting with Hydrocephalus and Epileptic Spasms
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SCIENTIFIC LETTER
Infantile Alexander Disease Presenting with Hydrocephalus and Epileptic Spasms Vykuntaraju K. Gowda 1
&
Varunvenkat M. Srinivasan 1 & Maya Bhat 2 & Chandrajit Prasad 2
Received: 1 October 2019 / Accepted: 19 February 2020 # Dr. K C Chaudhuri Foundation 2020
To the Editor: W Stewart Alexander described the first case of Alexander disease (AD) in a 15-mo-old child with megalencephaly, hydrocephalus and psychomotor retardation [1]. Here we describe an eight-mo-old infant with unusual presentation of hydrocephalus, epileptic spasms and neuroimaging changes with novel GFAP pathogenic variant. An eight-mo-old boy, born of non-consanguineous marriage with normal birth history, presented with developmental delay, large head, vomiting and seizures. The child had not attained social smile and head control. Initially seizures were generalized tonic-clonic seizures at four-mo and later epileptic spasms. Child underwent ventriculo-peritoneal (VP) shunt at four-mo of age for hydrocephalus. On examination, the head circumference was 43 cm, normal fundus of eye and spasticity were noted. The complete blood count, liver function test, renal function test, arterial blood gas analysis, serum ammonia, serum lactate, tandem mass spectrometry and gas chromatography mass spectrometry were all normal. EEG was suggestive of modified hypsarrhythmia. MRI of the brain showed asymmetrical T2 hyperintensities (right more than left) with frontal preponderance. The right frontal hyperintensity demonstrated inversion on FLAIR images. Post contrast T1WI showed extensive enhancement of bilateral caudate nuclei anterior putamina, fornices, right frontal lobar white and olfactory bulbs, tracts and subcallosal gyrus. The optic chiasm was thickened and demonstrated enhancement. Genetic testing by targeted next generation sequencing revealed a novel pathogenic heterozygous missense
* Vykuntaraju K. Gowda [email protected]
substitution (p.Asn77Asp) in Exon 1 of GFAP gene. Confirmation was done by Sanger sequencing for index case, and it was negative in both parents. Infantile AD presents before two-years of age with developmental delay, spastic paresis, macrocephaly and fatal clinical course. Sometimes, hydrocephalus or cerebral cavitation can be the presenting feature [2, 3]. The unusual finding in this child was asymmetric white matter involvement and enlargement and enhancement of olfactory bulbs and tracts. This case also had hydrocephalus similar to the case reported by Alexander et al. [1]. Requirement of VP shunt has been described by Ozkaya et al. [3]. Till date, only two reports of AD with West syndrome have been reported [4, 5]. The differential diagnosis for AD are childhood ataxia with CNS hypomyelination, megalencephalic leukoencephalopathy with subcortical cysts and Canavan disease. Based on MRI of brain we ruled out the above conditions. T he identifie d m issense substitution p.Asn77Asp alters a conserved residue in the protein. It lies in the coil 1A region of IF rod domain of the protein (73– 104 residues) an
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