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Primary Hyperoxaluria type 1 (PH) is a genetic disorder resulting from the hyperproduction of endogenous oxalate, caused by mutations in the AGXT gene. The disease results in increased serum and urinary levels of calcium oxalate, and consequent tissue deposit of oxalate crystals, lending to a progressive decline in renal function, and systemic oxalosis involving the kidneys, and other organs, including the heart. The present report describes a patient with PH1 oxalosis with postmortem analysis.
A female, caucasian, 19-years-old, diagnosed with bilateral medullary nephrocalcinosis at the age of three, with loss of medical follow-up, was admitted to the emergency department with uremia, anemia and depressed level of consciousness. Renal Replacement Therapy (RRT) was started. The genetic panel was performed and the diagnosis of PH1 was made, showing biallelic pathogenic variants in AGXT genes: c.33del and p.Lys12Argfs*34. Then, the cardiovascular screening was performed, which revealed: electrocardiogram with sinusal rhythm, signs of left atrial overload and left anterior superior divisional blockage. Echocardiogram with 13mm of posterior wall, and cardiac magnetic resonance indicated dilated heart chambers, excentric hypertrophy and important systolic dysfunction of the left ventricle with an ejection fraction of 34,9%, as well as important biatrial enlargement, aortic, mitral and tricuspid mild regurgitation; high levels of B-type natriuretic peptide over 5000pg/ml and also coronary artery calcium (CAC) score of zero (Agatston). This findings, specially the doppler echocardiography, was consistent with infiltrative cardiomyopathy. After about one year of RRT, the patient evolved to sudden death of unknown cause, and an autopsy was performed, indicating, as primary cause of death, pulmonary thromboembolism, secondary to previous cardiac dysfunction. On occasion, myocardial histopathological specimens were evaluated. The histopathological study showed cardiac muscle atrophy with oxalate deposits located in the cytoplasm of myocytes as well as intravascular and interstitial locations, pericardium and endocardium with no evidence of inflammatory activity.
The deposit of calcium oxalate crystals in the heart can lead to congestive heart failure, cardiac embolism and conduction disorders and all these cardiac findings are more frequent in patients in RRT. This case report brings to light the cardiac complications that may occur in patients with PH, but in this case, CAC zero. Nevertheless, the abnormalities described may be triggered by other factors, the cardiovascular deposit of oxalate in this case was hardly involved in the aggravation of the cardiac dysfunction.
PH is a rare disease and often under-recognized, resulting in delayed diagnosis and high morbidity and mortality, especially after end-stage kidney disease (ESKD) and systemic oxalosis already installed. The case described the features of cardiac oxalosis manifesting as a form of restrictive and infiltrative cardiomyopathy. We suggest that physicians should pay attention to these red flags of systemic diseases, oxalosis screening and cardiac status should promptly be evaluated as soon as suspected.