Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy
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...
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MDPI AG
2021-12-01
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| author | Agnieszka Ługowska Joanna K. Purzycka-Olewiecka Rafał Płoski Grażyna Truszkowska Maciej Pronicki Paulina Felczak Mateusz Śpiewak Aleksandra Podlecka-Piętowska Martyna Sitek Zofia T. Bilińska Przemysław Leszek Małgorzata Bednarska-Makaruk |
| author_facet | Agnieszka Ługowska Joanna K. Purzycka-Olewiecka Rafał Płoski Grażyna Truszkowska Maciej Pronicki Paulina Felczak Mateusz Śpiewak Aleksandra Podlecka-Piętowska Martyna Sitek Zofia T. Bilińska Przemysław Leszek Małgorzata Bednarska-Makaruk |
| author_sort | Agnieszka Ługowska |
| collection | DOAJ |
| description | 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 <i>TPP1</i> gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the <i>ABCD1</i> gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded <i>ABCD1</i> 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 <i>TPP1</i> gene. |
| first_indexed | 2024-03-10T01:07:49Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T01:07:49Z |
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| series | Life |
| spelling | doaj.art-d76e2f46eaf448258d98081a03af44592023-11-23T14:23:24ZengMDPI AGLife2075-17292021-12-01121310.3390/life12010003Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated CardiomyopathyAgnieszka Ługowska0Joanna K. Purzycka-Olewiecka1Rafał Płoski2Grażyna Truszkowska3Maciej Pronicki4Paulina Felczak5Mateusz Śpiewak6Aleksandra Podlecka-Piętowska7Martyna Sitek8Zofia T. Bilińska9Przemysław Leszek10Małgorzata Bednarska-Makaruk11Department of Genetics, Institute of Psychiatry and Neurology, Al. Sobieskiego 9, 02-957 Warsaw, PolandDepartment of Genetics, Institute of Psychiatry and Neurology, Al. Sobieskiego 9, 02-957 Warsaw, PolandDepartment of Medical Genetics, Medical University of Warsaw, ul. A. Pawińskiego 3c, 02-106 Warsaw, PolandMolecular Biology Laboratory, Department of Medical Biology, National Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, al. Dzieci Polskich 20, 04-730 Warsaw, PolandDepartment of Neuropathology, Institute of Psychiatry and Neurology, Al. Sobieskiego 9, 02-957 Warsaw, PolandMagnetic Resonance Unit, Department of Radiology, National Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw, PolandDepartment of Neurology, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warsaw, PolandDepartment of Neurology, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warsaw, PolandUnit for Screening Studies in Inherited Cardiovascular Diseases, National Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw, PolandDepartment of Heart Failure and Transplantology, National Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw, PolandDepartment of Genetics, Institute of Psychiatry and Neurology, Al. Sobieskiego 9, 02-957 Warsaw, PolandWe 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 <i>TPP1</i> gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the <i>ABCD1</i> gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded <i>ABCD1</i> 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 <i>TPP1</i> gene.https://www.mdpi.com/2075-1729/12/1/3tripeptidyl peptidase 1 (TPP1)ceroid lipofuscinosis 2 (CLN2)autosomal recessive spinocerebellar ataxia type 7 (SCAR7)dilated cardiomyopathycerebellar ataxia |
| spellingShingle | Agnieszka Ługowska Joanna K. Purzycka-Olewiecka Rafał Płoski Grażyna Truszkowska Maciej Pronicki Paulina Felczak Mateusz Śpiewak Aleksandra Podlecka-Piętowska Martyna Sitek Zofia T. Bilińska Przemysław Leszek Małgorzata Bednarska-Makaruk Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy Life tripeptidyl peptidase 1 (TPP1) ceroid lipofuscinosis 2 (CLN2) autosomal recessive spinocerebellar ataxia type 7 (SCAR7) dilated cardiomyopathy cerebellar ataxia |
| title | Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy |
| title_full | Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy |
| title_fullStr | Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy |
| title_full_unstemmed | Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy |
| title_short | Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy |
| title_sort | tripeptidyl peptidase 1 tpp1 deficiency in a 36 year old patient with cerebellar extrapyramidal syndrome and dilated cardiomyopathy |
| topic | tripeptidyl peptidase 1 (TPP1) ceroid lipofuscinosis 2 (CLN2) autosomal recessive spinocerebellar ataxia type 7 (SCAR7) dilated cardiomyopathy cerebellar ataxia |
| url | https://www.mdpi.com/2075-1729/12/1/3 |
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