Neuronal Ceroid Lipofuscinosis: Clinical and Laboratory Profile in Children from Tertiary Care Centre in South India

Abstract

Neuronal ceroid Lipofuscinosis (NCL), inherited disorders of lysosomal storage disorders, constitute the most common progressive encephalopathies with an incidence of 1.3 to 7 in 100,000 live births. We report clinical, electrophysiological, radiological, ultrastructural, and molecular genetic features of NCL. This is a retrospective review, in a tertiary care center from January 2016 to December 2019. All children with clinical features of NCL and confirmed by pathogenic mutation and/or enzyme assay were included. A total of 60 children (male:female = 3:1) were studied. The commonest type was CLN 2 (41.7%). Neuroregression, seizures, and ataxia were present in all cases. Retinal arterial attenuation was seen in 38.33% cases. Magnetic resonance imaging (MRI) brain was abnormal in all patients, thalamic and caudate nucleus atrophy common in CLN1 (62%). Electroencephalography was abnormal in all children, but photoparoxysmal response at low intermittent photic stimulation frequencies was seen in four children of CLN2. Electron microscopy done in 43 children revealed abnormal inclusions in 20 (46.52%) children. Enzyme study showed low levels in 36 (78%) out of 46 cases. Of these, 21 had low tripeptidyl peptidase and 15 had low palmitoyl protein thioesterase levels. Molecular testing done in 26 cases showed pathogenic variant in 23 (88%) cases. Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment and specific EEG changes are common in CLN2. These features are helpful in selecting enzyme assay for CLN1 versus CLN2. Electron microscopy helped in the diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.

Ceroid Lipofuscinosis in Children: Correspondence

“…Thus, a multimode approach played a role in the diagnosis of NCL." 1 We agree that observations in the present report might be clinically useful. Some clinical features might be more common in CLN1, whereas others are more common in CLN2.…”

“…We would like to share ideas on “Neuronal Ceroid Lipofuscinosis: Clinical and Laboratory Profile in Children from Tertiary Care Centre in South India.” 1 Prajapati et al noted that “Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment, and specific EEG changes are common … diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.” 1 We agree that observations in the present report might be clinically useful. Some clinical features might be more common in CLN1, whereas others are more common in CLN2.…”

Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients

“…Pathogenic mutations in CLN genes ( CLN1 , CLN2 , CLN3 , CLN5 , CLN6 , CLN7 , CLN8 , CLN10 , CLN13 , CLN14 , and CLCN2 ) represent the principle contribution among the investigated mutations, and affected patients were of age ranged from 2 to 11 years old. The main clinical features assigned to them were developmental regression, epilepsy, speech impairment, cognitive decline, vision loss, hypotonia, myoclonus, seizures, and ataxia, and their MRI scan showed cerebellar-cerebral atrophy [ 21 ]. Five novel homozygous missense mutations were reported in different genes of 5 unrelated patients; one of them c.600 G > A (p.Trp200Ser) was detected in CLN7 gene using the Sanger sequencing technique only, and the other 4 mutations c.872A > G (p.Gln 291 Arg), c.886G > C (p.Asp296His), c.446G > A (p.Gly149Asp), and (c.906 + 2 T > A) were described in genes CLN1 , CLN7 , CLN14 , and donor splice region of intron 11 of CLN3 gene, respectively, using WES.…”

Ceroid Lipofuscinosis in Children: Author's Reply

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We thank readers for critically evaluating our research study. 1 The queries raised are addressed below.We agree with reviewers' comments on clinical features that might not be able to discriminate and might not be helpful in selecting enzyme assay for CLN1 versus CLN2. Kamate et al reported that thalamic hypointensity is common in CLN1 similar to our cohort.

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“…We thank readers for critically evaluating our research study. 1 The queries raised are addressed below.…”