Exacerbation of erythropoietic protoporphyria by hyperthyroidism

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority of EPP patients present with a clinical symptom of painful phototoxicity. Liver damage, the most serious complication of EPP, occurs in <5% of the patients. This report describes a case of an EPP patient who complained of worsening cutaneous symptoms, nervousness, and insomnia. Laboratory tests showed highly increased protoporphyrin concentration in erythrocytes and elevated serum transaminases that are indicative of EPP-related liver damage. The subsequent finding of decreased serum thyroid-stimulating hormone (TSH) and increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the diagnosis of Graves' disease. The patient received 500MBq of radioiodine (I131). Three months after the radioactive iodine therapy, the thyroid volume was reduced to 30% of pretherapeutic volume. Although the patient was slightly hypothyroidic, his liver enzymes returned to normal, his erythrocytic protoporphyrin concentration dropped fivefold, and his skin symptoms improved dramatically. The coexistence of Graves' disease and EPP is a statistically rare event as, besides our patient, there was one additional case reported in the literature. Although the exact mechanism whereby Graves' disease interacts with EPP is yet to be explored, we recommend testing thyroid function in EPP patients with liver complication to exclude hyperthyroidism as a potential caus

Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: Risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P &lt; 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P &lt; 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis