Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants
Background Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited. Methods The clinical course of two brothers with pathogenic variants in the methio...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
08 October 2020
|
| In: |
Pediatric pulmonology
Year: 2020, Jahrgang: 55, Heft: 11, Pages: 3057-3066 |
| ISSN: | 1099-0496 |
| DOI: | 10.1002/ppul.25031 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ppul.25031 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.25031 
|
| Verfasserangaben: | Dominic Lenz, Mirjam Stahl, Elias Seidl, Dominik Schöndorf, Heiko Brennenstuhl, Florian Gesenhues, Tina Heinzmann, Thomas Longerich, Marisa I. Mendes, Holger Prokisch, Gajja S. Salomons, Carola Schön, Desirée E. C. Smith, Olaf Sommerburg, Matias Wagner, Jens H. Westhoff, Karl Reiter, Christian Staufner, Matthias Griese |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1939609755 | ||
| 003 | DE-627 | ||
| 005 | 20251028141145.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 251028s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ppul.25031 |2 doi | |
| 035 | |a (DE-627)1939609755 | ||
| 035 | |a (DE-599)KXP1939609755 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Lenz, Dominic |d 1984- |e VerfasserIn |0 (DE-588)1047559943 |0 (DE-627)778553914 |0 (DE-576)401159140 |4 aut | |
| 245 | 1 | 0 | |a Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants |c Dominic Lenz, Mirjam Stahl, Elias Seidl, Dominik Schöndorf, Heiko Brennenstuhl, Florian Gesenhues, Tina Heinzmann, Thomas Longerich, Marisa I. Mendes, Holger Prokisch, Gajja S. Salomons, Carola Schön, Desirée E. C. Smith, Olaf Sommerburg, Matias Wagner, Jens H. Westhoff, Karl Reiter, Christian Staufner, Matthias Griese |
| 246 | 3 | 0 | |a one |
| 246 | 3 | 3 | |a Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARSone variants |
| 264 | 1 | |c 08 October 2020 | |
| 300 | |a 10 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 28.10.2025 | ||
| 520 | |a Background Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited. Methods The clinical course of two brothers with pathogenic variants in the methionyl-tRNA synthetase (MARS)1 gene was compared to previously published patients. Functional studies in patient-derived fibroblasts were performed and therapeutic options evaluated. Results The younger brother was diagnosed with PAP at the age of 1 year. Exome sequencing revealed the homozygous MARS1 variant p.(Arg598Cys), leading to interstitial lung and liver disease (ILLD). At 2 years of age, following surgery hypoglycemia was detected, the pulmonary condition deteriorated, and the patient developed multiorgan failure. Six therapeutic whole lung lavages (WLL) were necessary to improve respiratory insufficiency. Methionine supplementation was started and a high protein diet ensured, leading to complete respiratory recovery. The older brother, homozygous for the same MARS1 variant, had a long-known distinct eating preference of methionine-rich food and showed a less severe clinical phenotype. Decreased aminoacylation activity confirmed the pathogenicity of p.(Arg598Cys) in vitro. In agreement with our review of currently published ILLD patients, the presence of hepatopathy, developmental delay, muscular hypotonia, and anemia support the multisystemic character of the disease. Conclusions Catabolic events can provoke a severe deterioration of the pulmonary situation in ILLD with a need for repetitive WLL. Although the precise role of oral methionine supplementation and high protein intake are unknown, we observed an apparent treatment benefit, which needs to be evaluated systematically in controlled trials. | ||
| 650 | 4 | |a interstitial lung and liver disease | |
| 650 | 4 | |a MARS1 | |
| 650 | 4 | |a methionine | |
| 650 | 4 | |a pulmonary alveolar proteinosis | |
| 650 | 4 | |a whole lung lavage | |
| 700 | 1 | |a Stahl, Mirjam |e VerfasserIn |0 (DE-588)1050007778 |0 (DE-627)783125836 |0 (DE-576)404265367 |4 aut | |
| 700 | 1 | |a Seidl, Elias |d 1986- |e VerfasserIn |0 (DE-588)1081689846 |0 (DE-627)846480395 |0 (DE-576)454669585 |4 aut | |
| 700 | 1 | |a Schöndorf, Dominik |d 1982- |e VerfasserIn |0 (DE-588)1212463013 |0 (DE-627)1701957728 |4 aut | |
| 700 | 1 | |a Brennenstuhl, Heiko |d 1987- |e VerfasserIn |0 (DE-588)1105686965 |0 (DE-627)862755344 |0 (DE-576)473681382 |4 aut | |
| 700 | 1 | |a Gesenhues, Florian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heinzmann, Tina Maria |d 1980- |e VerfasserIn |0 (DE-588)135747953 |0 (DE-627)570583721 |0 (DE-576)284550507 |4 aut | |
| 700 | 1 | |a Longerich, Thomas |d 1974- |e VerfasserIn |0 (DE-588)128494514 |0 (DE-627)373916124 |0 (DE-576)297178059 |4 aut | |
| 700 | 1 | |a Mendes, Marisa I. |e VerfasserIn |0 (DE-588)1370842929 |0 (DE-627)1929858582 |4 aut | |
| 700 | 1 | |a Prokisch, Holger |d 1966- |e VerfasserIn |0 (DE-588)118138596 |0 (DE-627)694704423 |0 (DE-576)291735126 |4 aut | |
| 700 | 1 | |a Salomons, Gajja S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schön, Carola |d 1967- |e VerfasserIn |0 (DE-588)137474040 |0 (DE-627)593172922 |0 (DE-576)303788429 |4 aut | |
| 700 | 1 | |a Smith, Desirée E. C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sommerburg, Olaf |d 1967- |e VerfasserIn |0 (DE-588)172907470 |0 (DE-627)69783543X |0 (DE-576)133762270 |4 aut | |
| 700 | 1 | |a Wagner, Matias |d 1988- |e VerfasserIn |0 (DE-588)1170833373 |0 (DE-627)1040131263 |0 (DE-576)512677778 |4 aut | |
| 700 | 1 | |a Westhoff, Jens |d 1976- |e VerfasserIn |0 (DE-588)129979295 |0 (DE-627)485304309 |0 (DE-576)297932497 |4 aut | |
| 700 | 1 | |a Reiter, Karl |e VerfasserIn |0 (DE-588)1243589752 |0 (DE-627)1774532468 |4 aut | |
| 700 | 1 | |a Staufner, Christian |d 1980- |e VerfasserIn |0 (DE-588)141097515 |0 (DE-627)703880950 |0 (DE-576)321299469 |4 aut | |
| 700 | 1 | |a Griese, Matthias |e VerfasserIn |0 (DE-588)17210565X |0 (DE-627)673143449 |0 (DE-576)167961292 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pediatric pulmonology |d New York, NY [u.a.] : Wiley-Liss, 1985 |g 55(2020), 11 vom: Okt., Seite 3057-3066 |h Online-Ressource |w (DE-627)302718818 |w (DE-600)1491904-7 |w (DE-576)079876676 |x 1099-0496 |7 nnas |a Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants |
| 773 | 1 | 8 | |g volume:55 |g year:2020 |g number:11 |g month:10 |g pages:3057-3066 |g extent:10 |a Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants |
| 856 | 4 | 0 | |u https://doi.org/10.1002/ppul.25031 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.25031 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20251028 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 141097515 |a Staufner, Christian |m 141097515:Staufner, Christian |d 910000 |d 910500 |e 910000PS141097515 |e 910500PS141097515 |k 0/910000/ |k 1/910000/910500/ |p 18 | ||
| 998 | |g 129979295 |a Westhoff, Jens |m 129979295:Westhoff, Jens |d 910000 |d 910500 |d 50000 |e 910000PW129979295 |e 910500PW129979295 |e 50000PW129979295 |k 0/910000/ |k 1/910000/910500/ |k 0/50000/ |p 16 |y j | ||
| 998 | |g 172907470 |a Sommerburg, Olaf |m 172907470:Sommerburg, Olaf |d 910000 |d 910500 |d 50000 |e 910000PS172907470 |e 910500PS172907470 |e 50000PS172907470 |k 0/910000/ |k 1/910000/910500/ |k 0/50000/ |p 14 | ||
| 998 | |g 128494514 |a Longerich, Thomas |m 128494514:Longerich, Thomas |d 910000 |d 912000 |e 910000PL128494514 |e 912000PL128494514 |k 0/910000/ |k 1/910000/912000/ |p 8 | ||
| 998 | |g 135747953 |a Heinzmann, Tina Maria |m 135747953:Heinzmann, Tina Maria |d 910000 |d 910500 |e 910000PH135747953 |e 910500PH135747953 |k 0/910000/ |k 1/910000/910500/ |p 7 | ||
| 998 | |g 1105686965 |a Brennenstuhl, Heiko |m 1105686965:Brennenstuhl, Heiko |d 910000 |d 910500 |e 910000PB1105686965 |e 910500PB1105686965 |k 0/910000/ |k 1/910000/910500/ |p 5 | ||
| 998 | |g 1212463013 |a Schöndorf, Dominik |m 1212463013:Schöndorf, Dominik |d 910000 |d 910500 |e 910000PS1212463013 |e 910500PS1212463013 |k 0/910000/ |k 1/910000/910500/ |p 4 | ||
| 998 | |g 1050007778 |a Stahl, Mirjam |m 1050007778:Stahl, Mirjam |d 50000 |e 50000PS1050007778 |k 0/50000/ |p 2 | ||
| 998 | |g 1047559943 |a Lenz, Dominic |m 1047559943:Lenz, Dominic |d 910000 |d 910500 |e 910000PL1047559943 |e 910500PL1047559943 |k 0/910000/ |k 1/910000/910500/ |p 1 |x j | ||
| 999 | |a KXP-PPN1939609755 |e 4792291259 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"display":"Lenz, Dominic","family":"Lenz","given":"Dominic","role":"aut"},{"given":"Mirjam","role":"aut","display":"Stahl, Mirjam","family":"Stahl"},{"given":"Elias","role":"aut","display":"Seidl, Elias","family":"Seidl"},{"given":"Dominik","role":"aut","family":"Schöndorf","display":"Schöndorf, Dominik"},{"display":"Brennenstuhl, Heiko","family":"Brennenstuhl","given":"Heiko","role":"aut"},{"given":"Florian","role":"aut","family":"Gesenhues","display":"Gesenhues, Florian"},{"display":"Heinzmann, Tina Maria","family":"Heinzmann","role":"aut","given":"Tina Maria"},{"display":"Longerich, Thomas","family":"Longerich","given":"Thomas","role":"aut"},{"given":"Marisa I.","role":"aut","display":"Mendes, Marisa I.","family":"Mendes"},{"given":"Holger","role":"aut","display":"Prokisch, Holger","family":"Prokisch"},{"given":"Gajja S.","role":"aut","family":"Salomons","display":"Salomons, Gajja S."},{"given":"Carola","role":"aut","display":"Schön, Carola","family":"Schön"},{"family":"Smith","display":"Smith, Desirée E. C.","role":"aut","given":"Desirée E. C."},{"family":"Sommerburg","display":"Sommerburg, Olaf","given":"Olaf","role":"aut"},{"role":"aut","given":"Matias","display":"Wagner, Matias","family":"Wagner"},{"family":"Westhoff","display":"Westhoff, Jens","role":"aut","given":"Jens"},{"role":"aut","given":"Karl","display":"Reiter, Karl","family":"Reiter"},{"role":"aut","given":"Christian","family":"Staufner","display":"Staufner, Christian"},{"family":"Griese","display":"Griese, Matthias","given":"Matthias","role":"aut"}],"titleAlt":[{"title":"Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARSone variants"}],"language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedDisp":"08 October 2020","dateIssuedKey":"2020"}],"note":["Gesehen am 28.10.2025"],"title":[{"title":"Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants","title_sort":"Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants"}],"id":{"doi":["10.1002/ppul.25031"],"eki":["1939609755"]},"recId":"1939609755","relHost":[{"id":{"issn":["1099-0496"],"zdb":["1491904-7"],"doi":["10.1002/(ISSN)1099-0496"],"eki":["302718818"]},"recId":"302718818","physDesc":[{"extent":"Online-Ressource"}],"disp":"Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variantsPediatric pulmonology","type":{"media":"Online-Ressource","bibl":"periodical"},"title":[{"title_sort":"Pediatric pulmonology","title":"Pediatric pulmonology"}],"origin":[{"publisherPlace":"New York, NY [u.a.]","publisher":"Wiley-Liss","dateIssuedKey":"1985","dateIssuedDisp":"1985-"}],"note":["Gesehen am 09.10.09"],"pubHistory":["1.1985 -"],"part":{"volume":"55","extent":"10","text":"55(2020), 11 vom: Okt., Seite 3057-3066","issue":"11","pages":"3057-3066","year":"2020"},"language":["eng"]}],"name":{"displayForm":["Dominic Lenz, Mirjam Stahl, Elias Seidl, Dominik Schöndorf, Heiko Brennenstuhl, Florian Gesenhues, Tina Heinzmann, Thomas Longerich, Marisa I. Mendes, Holger Prokisch, Gajja S. Salomons, Carola Schön, Desirée E. C. Smith, Olaf Sommerburg, Matias Wagner, Jens H. Westhoff, Karl Reiter, Christian Staufner, Matthias Griese"]},"physDesc":[{"extent":"10 S."}]} | ||
| SRT | |a LENZDOMINIRESCUEOFRE0820 | ||