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A Heart of Stone
Electronic Clinical Challenges and Images in GI A Heart of Stone Nirav Thosani,1 Mamoun Younes,2 and Jen-Jung Pan1 1
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, and 2Department of Pathology, The University of Texas Medical School at Houston, Texas
Question: A 33-year-old woman with past medical history of hypertension, coronary artery disease with congestive heart failure and end-stage renal disease (ESRD) was admitted with worsening bilateral lower extremity pain. She had a longstanding history of recurrent kidney stones since age 12 and ultimately developed ESRD at the age of 27. Over the last 6 months, she developed worsening peripheral vascular disease with diffuse ulcerations with eschar formation over bilateral feet and legs (Figure A) and presented to our institution. Abdominal x-ray showed extensive nephrocalcinosis of bilateral kidneys (Figure B). Angiography of bilateral lower extremities (Figure C) showed narrowing of the arteries with beading appearance in the medium and small size arteries in bilateral legs. There was bilateral, near-complete occlusion of tibial vessels at the level of ankle and minimal flow into the foot. She underwent skin punch biopsy from the left lower extremity that showed near-complete necrosis affecting the epidermis, dermis, and subcutis. Crystalline refractile polarizable material was seen deposited in the walls of the subcutaneous blood vessels with luminal occlusion (Figure D). What is the diagnosis? See the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Conflicts of interest: The authors disclose no conflicts. © 2013 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.03.026
GASTROENTEROLOGY 2013;145:e6–e7
Electronic Clinical Challenges and Images in GI, continued Answer to the Clinical Challenges and Images in GI Question: Image 3: Primary Hyperoxaluria Type 1
Crystalline refractile deposits on skin punch biopsy did not have the basophilic staining quality of calcium phosphate on hematoxylin and eosin staining and were consistent with calcium oxalate deposition. She was found to have elevated urinary excretion of glycolic acid and oxalic acid and her ABXT gene analysis showed pathologic mutation with homozygous sequence change diagnostic for primary hyperoxaluria type 1 (PH1). She had ischemic gangrene of both lower extremities owing to severe peripheral vascular disease and died during the process of combined liver–kidney transplant evaluation owing to septic shock and multiorgan failure. Autopsy revealed bipyramidal octahedral “envelopes” calcium oxalate dihydrate crystals within the media of coronary arteries and aorta, myocytes and vessels within myocytes (Figure E), within tubules of kidneys (Figure F), within hepatic vessels and cardiac cirrhosis (Figure G), within vessels in pancreas with autolysis (Figure H), within muscularis propria of gastrointestinal tract (Figure I), within skeletal muscles vessels (Figure J), and skin. Her brother, also with a history of ESRD, was found to have PH1 on screening and underwent combines liver and kidney transplantation with favorable outcome. PH1 is a rare, peroxisomal disorder characterized by hepatic enzymatic deficiency of alanine glyoxylate aminotransferase.1 PH1 is a rare disease with incidence rate of 4–10:1,000,000.2 In PH1, supersaturation of urine with oxalate leads to nephrolithiasis/nephrocalcinosis and eventually ESRD. When the glomerular filtration rate is <25, without any intervention, patients suffer from systemic oxalosis with oxalate deposition in kidneys, bone and bone marrow, retina, myocardium, blood vessels, peripheral nerves, skin, and subcutaneous tissues. Liver transplantation with or without kidney transplantation, depending on the extent of organ involvement, helps to restore organ function and prolong life.3 Early diagnosis remains the key to successfully managing this potentially curable disease, thus making awareness amongst clinicians vital for patient care. References 1. Coulter-Mackie MB, White CT, Hurley RM, et al. Primary hyperoxaluria type 1. In: GeneReviews. Seattle: University of Washington, 1993. 2. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics 2000; 105:e10. 3. Bergstralh EJ, Monico CG, Lieske JC, et al. Transplantation outcomes in primary hyperoxaluria. Am J Transplant 2010; 10:2493–2501.
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Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, and 2Department of Pathology, The University of Texas Medical School at Houston, Texas
Question: A 33-year-old woman with past medical history of hypertension, coronary artery disease with congestive heart failure and end-stage renal disease (ESRD) was admitted with worsening bilateral lower extremity pain. She had a longstanding history of recurrent kidney stones since age 12 and ultimately developed ESRD at the age of 27. Over the last 6 months, she developed worsening peripheral vascular disease with diffuse ulcerations with eschar formation over bilateral feet and legs (Figure A) and presented to our institution. Abdominal x-ray showed extensive nephrocalcinosis of bilateral kidneys (Figure B). Angiography of bilateral lower extremities (Figure C) showed narrowing of the arteries with beading appearance in the medium and small size arteries in bilateral legs. There was bilateral, near-complete occlusion of tibial vessels at the level of ankle and minimal flow into the foot. She underwent skin punch biopsy from the left lower extremity that showed near-complete necrosis affecting the epidermis, dermis, and subcutis. Crystalline refractile polarizable material was seen deposited in the walls of the subcutaneous blood vessels with luminal occlusion (Figure D). What is the diagnosis? See the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Conflicts of interest: The authors disclose no conflicts. © 2013 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.03.026
GASTROENTEROLOGY 2013;145:e6–e7
Electronic Clinical Challenges and Images in GI, continued Answer to the Clinical Challenges and Images in GI Question: Image 3: Primary Hyperoxaluria Type 1
Crystalline refractile deposits on skin punch biopsy did not have the basophilic staining quality of calcium phosphate on hematoxylin and eosin staining and were consistent with calcium oxalate deposition. She was found to have elevated urinary excretion of glycolic acid and oxalic acid and her ABXT gene analysis showed pathologic mutation with homozygous sequence change diagnostic for primary hyperoxaluria type 1 (PH1). She had ischemic gangrene of both lower extremities owing to severe peripheral vascular disease and died during the process of combined liver–kidney transplant evaluation owing to septic shock and multiorgan failure. Autopsy revealed bipyramidal octahedral “envelopes” calcium oxalate dihydrate crystals within the media of coronary arteries and aorta, myocytes and vessels within myocytes (Figure E), within tubules of kidneys (Figure F), within hepatic vessels and cardiac cirrhosis (Figure G), within vessels in pancreas with autolysis (Figure H), within muscularis propria of gastrointestinal tract (Figure I), within skeletal muscles vessels (Figure J), and skin. Her brother, also with a history of ESRD, was found to have PH1 on screening and underwent combines liver and kidney transplantation with favorable outcome. PH1 is a rare, peroxisomal disorder characterized by hepatic enzymatic deficiency of alanine glyoxylate aminotransferase.1 PH1 is a rare disease with incidence rate of 4–10:1,000,000.2 In PH1, supersaturation of urine with oxalate leads to nephrolithiasis/nephrocalcinosis and eventually ESRD. When the glomerular filtration rate is <25, without any intervention, patients suffer from systemic oxalosis with oxalate deposition in kidneys, bone and bone marrow, retina, myocardium, blood vessels, peripheral nerves, skin, and subcutaneous tissues. Liver transplantation with or without kidney transplantation, depending on the extent of organ involvement, helps to restore organ function and prolong life.3 Early diagnosis remains the key to successfully managing this potentially curable disease, thus making awareness amongst clinicians vital for patient care. References 1. Coulter-Mackie MB, White CT, Hurley RM, et al. Primary hyperoxaluria type 1. In: GeneReviews. Seattle: University of Washington, 1993. 2. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics 2000; 105:e10. 3. Bergstralh EJ, Monico CG, Lieske JC, et al. Transplantation outcomes in primary hyperoxaluria. Am J Transplant 2010; 10:2493–2501.
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