Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation
Background: Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was admitted because of refractory angina, which he had had since the age of 30 years, micro-hematuria, and recurrent transitory...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/22/7150 |
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| author | Andrea Frustaci Rosario Cianci Romina Verardo Bruna Cerbelli Maria Cecilia D’Asdia Alessandro De Luca |
| author_facet | Andrea Frustaci Rosario Cianci Romina Verardo Bruna Cerbelli Maria Cecilia D’Asdia Alessandro De Luca |
| author_sort | Andrea Frustaci |
| collection | DOAJ |
| description | Background: Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was admitted because of refractory angina, which he had had since the age of 30 years, micro-hematuria, and recurrent transitory ischemic attacks from the age of 64. Methods: Hematochemical studies, ECG, Holter monitoring, 2D-echo, cardiac magnetic resonance (CMR), CTA of cerebral vessels, endomyocardial coronary angiography, and kidney biopsy processes were undertaken. Gene mutation analysis was conducted using next-generation sequencing, which included more than 5000 genes associated with inherited diseases. Results: Hematochemical findings were unremarkable. The ECG, Holter, 2D-echo, and CTA of brain vessels were normal. Cerebral magnetic resonance showed the presence of multiple small foci of ischemia. Coronary and ventricular angiography showed normal arteries with remarkably slow flow and multiple biventricular micro-aneurysms. At the endomyocardial biopsy, five of seven arterioles presented severe lumen obstruction due to hypertrophy and disarray of the muscular coat. Similarly, obstructed pre-glomerular arteries with glomerular sclerosis were seen at the renal biopsy. Genetics identified mutations in the ABCC6, MMP2, and XYLT1 genes, which play pivotal roles in the extracellular matrix. Conclusion: This study described a new genetic microvascular obstructive disease causing progressive hypo-perfusion of the human brain, heart, and kidney. |
| first_indexed | 2024-03-09T16:43:19Z |
| format | Article |
| id | doaj.art-bd0e2488c04a4018832cc44f14cec14c |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T16:43:19Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-bd0e2488c04a4018832cc44f14cec14c2023-11-24T14:49:39ZengMDPI AGJournal of Clinical Medicine2077-03832023-11-011222715010.3390/jcm12227150Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral CirculationAndrea Frustaci0Rosario Cianci1Romina Verardo2Bruna Cerbelli3Maria Cecilia D’Asdia4Alessandro De Luca5IRCCS San Raffaele, Via di Val Cannuta, 247, 00166 Rome, ItalyHead of Nephrological “Dh and Day-Service Unit”, Policlinic Umberto I, Sapienza University of Rome, 00161 Rome, ItalyCellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, 00149 Rome, ItalyDepartment of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, 00161 Rome, ItalyMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyBackground: Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was admitted because of refractory angina, which he had had since the age of 30 years, micro-hematuria, and recurrent transitory ischemic attacks from the age of 64. Methods: Hematochemical studies, ECG, Holter monitoring, 2D-echo, cardiac magnetic resonance (CMR), CTA of cerebral vessels, endomyocardial coronary angiography, and kidney biopsy processes were undertaken. Gene mutation analysis was conducted using next-generation sequencing, which included more than 5000 genes associated with inherited diseases. Results: Hematochemical findings were unremarkable. The ECG, Holter, 2D-echo, and CTA of brain vessels were normal. Cerebral magnetic resonance showed the presence of multiple small foci of ischemia. Coronary and ventricular angiography showed normal arteries with remarkably slow flow and multiple biventricular micro-aneurysms. At the endomyocardial biopsy, five of seven arterioles presented severe lumen obstruction due to hypertrophy and disarray of the muscular coat. Similarly, obstructed pre-glomerular arteries with glomerular sclerosis were seen at the renal biopsy. Genetics identified mutations in the ABCC6, MMP2, and XYLT1 genes, which play pivotal roles in the extracellular matrix. Conclusion: This study described a new genetic microvascular obstructive disease causing progressive hypo-perfusion of the human brain, heart, and kidney.https://www.mdpi.com/2077-0383/12/22/7150microvascular dysplasiageneticanginaischemia |
| spellingShingle | Andrea Frustaci Rosario Cianci Romina Verardo Bruna Cerbelli Maria Cecilia D’Asdia Alessandro De Luca Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation Journal of Clinical Medicine microvascular dysplasia genetic angina ischemia |
| title | Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation |
| title_full | Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation |
| title_fullStr | Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation |
| title_full_unstemmed | Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation |
| title_short | Novel Genetic Microvascular Dysplasia Causing Hypoperfusion of Cardiac, Renal, and Cerebral Circulation |
| title_sort | novel genetic microvascular dysplasia causing hypoperfusion of cardiac renal and cerebral circulation |
| topic | microvascular dysplasia genetic angina ischemia |
| url | https://www.mdpi.com/2077-0383/12/22/7150 |
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