Position of Experts Regarding Follow-Up of Patients with Neuronal Ceroid Lipofuscinosis-2 Disease in Latin America

Guelbert, Norberto; Atanacio, Nora; Denzler, Inés; Embiruçu, Emília Katiane; Mancilla, Nury; Naranjo, Ricardo; Pessoa, André Luiz Santos; Spécola, Norma; Tavera-Saldaña, Lina Marcela; Troncoso, Mónica; Vergara, Diane

doi:10.1590/2326-4594-jiems-2020-0012

Cited by 3 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to Guelbert et al, cardiac anomalies and conduction disorders can be caused by the storage of lipopigments found not only in the neurons but also in other tissues, including the heart [31]. Opposite to this, the curvilinear or fingerprint bodies were absent in heart sample from our patient.…”

Section: Discussionsupporting

confidence: 42%

Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy

Ługowska

Purzycka-Olewiecka

Płoski

et al. 2021

Life

View full text Add to dashboard Cite

We report on a 36-year-old man with cerebellar-extrapyramidal syndrome and severe heart failure because of dilated cardiomyopathy of unknown origin. Dysarthria and cardiac arrhythmia began at early childhood (4 years of age). Brain MRI (28 years of age) demonstrated severe cerebellar atrophy. At the age 32, he presented with dysarthria, ataxia, dystonia, and tremor of the right hand, bilateral slowed neural conduction in the visual pathways, and decreased mental acuity. At the age of 33 years, the patient underwent cardiac transplantation because of severe dilated cardiomyopathy. In the TPP1 gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the ABCD1 gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded ABCD1 mutation as the pathogenic one. Tripeptidyl peptidase 1 (TPP1) activity was reduced (8,8 U/mg protein/h; reference range: 47.4 ± 10.7). In light microscopy the biopsy specimens obtained from explanted heart showed severe myocyte hypertrophy with perinuclear vacuolization with inclusions. Electron microscopy revealed absence of lipofuscin accumulation, no ultrastructural curvilinear profiles, fingerprint bodies, or granular osmiophilic deposits (GRODs) in lysosomes. As described here, the patient presents clinical symptoms observed in benign forms of ceroid lipofuscinosis type 2 (CLN2) and simultaneously some features of autosomal recessive spinocerebellar ataxia type 7 (SCAR7), which is also caused by mutations in the TPP1 gene.

show abstract

Section: Discussionsupporting

confidence: 42%

Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy

Ługowska

Purzycka-Olewiecka

Płoski

et al. 2021

Life

View full text Add to dashboard Cite

show abstract

“…Furthermore, 1/51 had a variant Juvenile CLN1 disease phenotype, and 1/51 a variant congenital CLN8 disease phenotype (Figure 4). [8,17,18,22,27,28, These variant phenotypes and their genotypes are described in the present study. Another 16/51 individuals showed other genotypes (CLN3, CLN5, CLN6, and CLN7 genes) and remain out of the scope of this paper.…”

Section: Resultsmentioning

confidence: 72%

“…Individuals with the most frequent LINCL or "classical" CLN2 phenotype either with the most common DNA variants c.622C>T and c.509-1G>C in homozygous or heterozygous combinations [9] or with other less frequent DNA variants described and published of the Cordoba cohort in individuals with the "classical" phenotypes. [8,27] and/or the B platform (Bitgenia, Buenos Aires, Argentina; https://apps2.bitgenia.com/). DNA variants were classified following the considerations of the American College of Medical Genetics and Genomics (ACMG).…”

Section: Subjectsmentioning

confidence: 99%

“…gov/snp/, GeneCards https://www.genecards.org/, and NCL Resource https://www.ucl.ac.uk/ncl-disease/. Those DNA variants with high pathogenic significance were validated by PCR-Sanger sequencing in a new sample as described elsewhere [8,15,22,24,27,28]. DNA variants were encoded according to the following Genbank transcript sequences: NM_000310 for the PPT1/CLN1 gene, NM_000391 for the…”

mentioning

confidence: 99%

See 1 more Smart Citation

“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era

Pesaola

Guelbert

Venier

et al. 2021

J. inborn errors metab. screen.

Self Cite

View full text Add to dashboard Cite

show abstract

“…These differences among Latin American subjects clinical and imaging phenotypes and other cohorts deserve further research. CLN2 disease is the most common form of lipofuscinosis in South America; a later onset of symptoms and slower neurodegenerative progression, when compared with the classical form, may account for more than 50% of the cases described in our region, unlike other areas of the world [15]. Wide genetic mix and the finding of different mutations and deletions observed in South America may explain this difference [15].…”

Section: Discussionmentioning

confidence: 93%

Neuronal Ceroid Lipofuscinosis Type 2: A Case Series from Argentina

Guelbert

2022

J. inborn errors metab. screen.

Self Cite

View full text Add to dashboard Cite

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CLN2/TPP1 gene, leading to a deficiency in tripeptidyl peptidase 1 activity. Enzyme replacement therapy with cerliponase alfa (recombinant human TPP1 [rhTPP1]; Brineura®) was approved in the United States and Europe for the treatment of CLN2 disease in 2017. We retrospectively report a cohort of 19 patients with CLN2 assisted in a specialized center in Argentina, including 8 newly diagnosed cases. Speech disorders and white matter changes/ventricular system enlargement were the most frequent clinical and imaging findings at CLN2 disease onset, respectively. Patients treated with cerliponase alfa presented a stable or improved course of the disease in this Latin American real world setting, as described in clinical trials.

show abstract

Position of Experts Regarding Follow-Up of Patients with Neuronal Ceroid Lipofuscinosis-2 Disease in Latin America

Cited by 3 publications

References 35 publications

Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy

Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy

“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era

Neuronal Ceroid Lipofuscinosis Type 2: A Case Series from Argentina

Contact Info

Product

Resources

About