Thrombotic microangiopathy following heart transplant in pediatric Danon disease.

Published on Jun 1, 2020in Pediatric Transplantation1.425
· DOI :10.1111/PETR.13669
Kevin Hummel2
Estimated H-index: 2
(UofU: University of Utah),
Kristi Glotzbach1
Estimated H-index: 1
(UofU: University of Utah)
+ 2 AuthorsAshwin K. Lal9
Estimated H-index: 9
(UofU: University of Utah)
This case describes an uncommon acute complication of diffuse thrombotic angiopathy and associated aHUS/TTP in an 11-year-old girl with Danon disease who underwent orthotopic heart transplant. Shortly after transplant, despite an uncomplicated operative course, the patient developed severe kidney injury and progressive altered mental status, culminating in cerebral edema, brain herniation, and death. She had received a single dose of tacrolimus (FK506) and a single dose of antithymocyte globulin. Sources of progressive somnolence, including oversedation from impaired renal clearance of opiates, and severe myopathy as has been previously described in Danon disease, were ruled out, and the patient continued to decline. Initial brain CT scan early after transplant showed no signs of cerebral edema, but repeat CT indicated severe cerebral edema. Based on autopsy, diffuse thrombotic angiopathy, with signs of hemolytic anemia with schistocytes, was likely responsible for her deterioration in the broader condition of aHUS/TTP.
📖 Papers frequently viewed together
2 Citations
13 Citations
1 Citations
#1Michela Brambatti (UCSD: University of California, San Diego)H-Index: 13
#2Oren Caspi (UCSD: University of California, San Diego)H-Index: 19
Last. Eric Adler (UCSD: University of California, San Diego)H-Index: 25
view all 7 authors...
Abstract Background Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy, characterized by high penetrance and severe cardiomyopathy. Because of its rarity, the natural history (NH) is uncertain. Objectives We aimed to describe disease variability and outcomes through a systematic review of all published DD cases. Methods Among 83 manuscripts in MEDLINE and EMBASE on DD cases published until October 2017, we identified 146 patients with positive genetic testing for DD or positive m...
25 CitationsSource
#1Vidhya Nair (U of O: University of Ottawa)H-Index: 3
#2Eric C. Belanger (U of O: University of Ottawa)H-Index: 16
Last. John P. Veinot (U of O: University of Ottawa)H-Index: 37
view all 3 authors...
Abstract Lysosomal storage disorders (LSD) comprise a group of diseases caused by a deficiency of lysosomal enzymes, membrane transporters or other proteins involved in lysosomal biology. Lysosomal storage disorders result from an accumulation of specific substrates, due to the inability to break them down. The diseases are classified according to the type of material that is accumulated; for example, lipid storage disorders, mucopolysaccharidoses and glycoproteinoses. Cardiac disease is particu...
22 CitationsSource
Hemolytic uremic syndrome (HUS) is a triad of thrombocytopenia, microangiopathic hemolysis, and acute kidney injury, within the broader category of thrombotic microangiopathy (TMA). The most common form of HUS in children is due to Shigatoxin-producing E. coli infection, although other forms due to invasive pneumococcal disease, genetic defects in complement regulation, and cobalamin C metabolism also occur. As the many forms of TMA share overlapping clinical features through the common pathomec...
31 CitationsSource
#1Daniel Oren (Semmelweis University)H-Index: 2
#2Peter Chau (LLUMC: Loma Linda University Medical Center)H-Index: 1
Last. Seth A. Hollander (Stanford University)H-Index: 13
view all 8 authors...
: Danon disease (DD) is an X-linked dominant disorder caused by a mutation in the lysosomal-associated membrane protein-2 (LAMP-2) gene coding for the LAMP-2 protein. We report two cases of successful heart transplantation (HT) in adolescent brothers with DD, including one who was bridged to HT for 34 days with a HeartWare left ventricular assist device. In both patients, the post-transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal....
5 CitationsSource
#1Christine MacDonald (U of A: University of Alberta)H-Index: 1
#2Colleen M. Norris (U of A: University of Alberta)H-Index: 45
Last. Catherine Morgan (U of A: University of Alberta)H-Index: 17
view all 6 authors...
Background Critical illness following heart transplantation can include acute kidney injury (AKI). Study objectives were to define the epidemiology of, risk factors for, or impact on outcomes of AKI after pediatric heart transplant.
25 CitationsSource
#1Wendy Lim (McMaster University)H-Index: 44
#2Sara K. Vesely (University of Oklahoma Health Sciences Center)H-Index: 67
Last. James N. George (University of Oklahoma Health Sciences Center)H-Index: 81
view all 3 authors...
A 40-year-old obese black woman developed abdominal pain with progressive generalized weakness over several days. Physical examination was normal except for several small bruises on her extremities. Laboratory data revealed the following: hemoglobin, 5.0 g/dL; platelet count, 4000/µL; creatinine, 0
84 CitationsSource
#1Spero R. Cataland (OSU: Ohio State University)H-Index: 31
#2Haifeng M. Wu (OSU: Ohio State University)H-Index: 22
Abstract The increased understanding of the pathophysiology of both atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP) in recent years has led to significant therapeutic advances for both conditions. These advances have placed an increased emphasis on a more rapid differentiation of both disorders which remain clinical diagnoses. In particular, recent data demonstrating the effectiveness of complement inhibition in patients with aHUS have increased the need f...
33 CitationsSource
#2Karina LopesH-Index: 2
Last. Mário CamposH-Index: 8
view all 6 authors...
2 CitationsSource
#1Pieter van der Starre (Stanford University)H-Index: 7
#2Tobias Deuse (Stanford University)H-Index: 27
Last. Philip E. Oyer (Stanford University)H-Index: 75
view all 6 authors...
Introduction: Postoperative muscle weakness is a serious complication in surgical intensive care patients. It is mostly described as critical illness polyneuromyopathy. Risk factors include intensive care length of stay, sepsis, poor glycemic control, and combined use of corticosteroids and neuromuscular blocking agents, malnutrition, and electrolyte imbalance. Methods: We report a case of late-progressive, profound weakness after heart transplantation for noncompaction cardiomyopathy which requ...
27 CitationsSource
#1Gina Zini (CUA: The Catholic University of America)H-Index: 25
#2Giuseppe D'Onofrio (CUA: The Catholic University of America)H-Index: 16
Last. Jean-François LesesveH-Index: 12
view all 10 authors...
SUMMARY Schistocytes are fragments of red blood cells (RBCs) produced by extrinsic mechanical damage within the circulation. The detection of schistocytes is an important morphological clue to the diagnosis of thrombotic microangiopathic anemia (TMA). Reporting criteria between different laboratories, however, are not uniform, owing to variability of shape and nature of fragments, as well as subjectivity and heterogeneity in their morphological assessment. Lack of standardization may lead to inc...
105 CitationsSource
Cited By1
#2Seetha Radhakrishnan (U of T: University of Toronto)H-Index: 5
Last. Seema Mital (U of T: University of Toronto)H-Index: 49
view all 4 authors...