Expanding the phenotype of the rare Neuronal Ceroid Lipofuscinoses (NCL) 10 Di Maggio C1, Bernardini L2, Masuelli L4, Aiello C5, Giorgi D3, Pollini L1, Torres B2, Bertini E S5, Leuzzi V1 1Dept HumNeurosc, Univ Sapienza, Rome, Italy, 2Cytogen Unit, IRCCS Casa Sollievo Soffer, San Giovanni Rotondo (FG), Italy, 3Dept Head- Neck, Div Ophth, Univ Sapienza, Rome, Italy, 4Dept Experimental Med, Univ Sapienza, Rome, Italy, 5Unit Musc Neur Dis, Bam Ges Childr Hosp, Rome, Italy Background:NCL type 10 is caused by a deficiency in cathepsin D (CTSD), a lysosomal protease involved in proteolytic degradation, cell invasion and apoptosis, which results in a severe congenital phenotype with rapid progression to exitus and a milder form with a later onset with ataxia, dementia and retinopathy. Case Report: This 3,5-year-old girl was born from consanguineous parents after a pregnancy complicated by fetal ascites since the 6th month. Previous pregnancies were normal. She presented development delay during the first months of life. Neurological regression was observed at 26 months of life. At 28 months she showed: facial dysmorphism, acquired microcephaly, apostural status with profound hypotonia, unresponsiveness to visual stimulation. EEG showed a multifocal epileptic pattern. Brain MRI showed a generalized cortical atrophy. On CSF examination folate was low (43.2 nmol/L; r.v. 63–111). An extensive neurometabolic work-up failed to detect any alteration. She eventually developed optic atrophy with “salt and pepper” retinopathy. ERGwere not evocable. Echocardiogram revealed a slight thickening of the interventricular septum. Ultrastructural analysis of the skin detected vacuolated fibroblasts, osmophilic deposits, fingerprint-like structures, lipopigment storage in the cytoplasm of a lymphocyte, suggesting NCL. Results: SNP-array analysis was negative for CNVs but disclosed a high rate of regions of homozygosity(about 9%; ROH), among which a ROH of about 3.5 Mb within 11p15.511p15.4 genomic region,including NCL10 locus (CTSD gene). NGS panel for NCL detected a homozygous causative variant in CTSD gene (c.308T>A; p. L103Q). Discussion: With respect to other patients so far reported (11) our case presents an intermediate phenotype and age of onset. Heart involvement, reported in several NCL types, is emerging as a possible second target of the disease. Further study is required to support CSF folate as a metabolic biomarker of the disease.
Expanding the phenotype of the rare neuronal ceroid lipofuscinoses (ncl) 10 / Di Maggio, C; Bernardini, L; Masuelli, L; Aiello, Chiara; Giorgi, D; Pollini, L; Torres, B; Bertini Enrico, Silvio; Leuzzi, V. - (2018). (Intervento presentato al convegno SSIEM 2018: Annual Symposium of the Society for the Study of Inborn Errors of Metabolism, Athens, Greece, 4-7 September 2018 tenutosi a Athens, Greece).
Expanding the phenotype of the rare neuronal ceroid lipofuscinoses (ncl) 10
Di Maggio C;Masuelli L;Pollini L;Torres B;Leuzzi V
2018
Abstract
Expanding the phenotype of the rare Neuronal Ceroid Lipofuscinoses (NCL) 10 Di Maggio C1, Bernardini L2, Masuelli L4, Aiello C5, Giorgi D3, Pollini L1, Torres B2, Bertini E S5, Leuzzi V1 1Dept HumNeurosc, Univ Sapienza, Rome, Italy, 2Cytogen Unit, IRCCS Casa Sollievo Soffer, San Giovanni Rotondo (FG), Italy, 3Dept Head- Neck, Div Ophth, Univ Sapienza, Rome, Italy, 4Dept Experimental Med, Univ Sapienza, Rome, Italy, 5Unit Musc Neur Dis, Bam Ges Childr Hosp, Rome, Italy Background:NCL type 10 is caused by a deficiency in cathepsin D (CTSD), a lysosomal protease involved in proteolytic degradation, cell invasion and apoptosis, which results in a severe congenital phenotype with rapid progression to exitus and a milder form with a later onset with ataxia, dementia and retinopathy. Case Report: This 3,5-year-old girl was born from consanguineous parents after a pregnancy complicated by fetal ascites since the 6th month. Previous pregnancies were normal. She presented development delay during the first months of life. Neurological regression was observed at 26 months of life. At 28 months she showed: facial dysmorphism, acquired microcephaly, apostural status with profound hypotonia, unresponsiveness to visual stimulation. EEG showed a multifocal epileptic pattern. Brain MRI showed a generalized cortical atrophy. On CSF examination folate was low (43.2 nmol/L; r.v. 63–111). An extensive neurometabolic work-up failed to detect any alteration. She eventually developed optic atrophy with “salt and pepper” retinopathy. ERGwere not evocable. Echocardiogram revealed a slight thickening of the interventricular septum. Ultrastructural analysis of the skin detected vacuolated fibroblasts, osmophilic deposits, fingerprint-like structures, lipopigment storage in the cytoplasm of a lymphocyte, suggesting NCL. Results: SNP-array analysis was negative for CNVs but disclosed a high rate of regions of homozygosity(about 9%; ROH), among which a ROH of about 3.5 Mb within 11p15.511p15.4 genomic region,including NCL10 locus (CTSD gene). NGS panel for NCL detected a homozygous causative variant in CTSD gene (c.308T>A; p. L103Q). Discussion: With respect to other patients so far reported (11) our case presents an intermediate phenotype and age of onset. Heart involvement, reported in several NCL types, is emerging as a possible second target of the disease. Further study is required to support CSF folate as a metabolic biomarker of the disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
