Acute intermittent porphyria in adults: a clinical case

Background. Porphyria unites genetic pathologies related to abnormal haem (an intermediate product of haemoglobin metabolism) synthesis and its toxic products accumulation in human body. Symptoms can vary, from photosensitivity, skin rashes and chronic abdominal pain towards partial or complete paralysis and acute psychosis. This metabolic disorder is diagnosed with molecular genetic and laboratory biosample tests. Drug therapy aims at reducing toxic metabolites concentration in patient’s blood.Clinical Case Description. A 28-yo female patient had an acute atypical porphyria attack with a later onset of neurovisceral manifestations (acute abdominal pain, tachycardia) progressing post-drug-treatment into acute sensorimotor polyneuropathy with flaccid, predominantly proximal, hands-prevalent tetraparaesis. Biochemical urine tests at the National Research Center for Hematology (by 30.06.2020) revealed porphobilinogen 55.3 mg/L at norm <3. Vital indications required an urgent haem arginate pathogenetic therapy (Normosang) in a 4-day course of 3 mg/kg/day drop infusion. The recommended course was well tolerated. Drug therapy and rehabilitation entailed a positive dynamics of restoring limb muscle strength towards an almost easy getting-up from chair and bed, and skin lightening. The patient was discharged on day 20 with diagnosis: “Acute intermittent porphyria. Axonal-demyelinating sensorimotor polyneuropathy. Severe flaccid asymmetric predominantly proximal hands-prevalent tetraparaesis. Subacute course, stabilisation phase. Condition after one course of haem arginate pathogenetic therapy (Normosang) at 3 mg/kg/day”. A resident haematologist surveillance was recommended, with a routine referral for inpatient examination and treatment at the Department of Orphan Diseases of the National Research Center for Hematology, Ministry of Health of Russia.Conclusion. Porphyria is relatively rarely diagnosed, about 12 cases per 100,000 people. The symptoms variety and nonspecificity conduce to a low detection rate, and untimely diagnoses can entail severe clinical manifestations, including lethal outcomes

Hypoxic Stress Decreases c-Myc Protein Stability in Cardiac Progenitor Cells Inducing Quiescence and Compromising Their Proliferative and Vasculogenic Potential

Abstract Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration and improve heart function. However, evidence suggests that their regenerative capacity may be limited in conditions of severe hypoxia. Elucidating the mechanisms involved in CPC protection against hypoxic stress is essential to maximize their cardioprotective and therapeutic potential. We investigated the effects of hypoxic stress on CPCs and found significant reduction in proliferation and impairment of vasculogenesis, which were associated with induction of quiescence, as indicated by accumulation of cells in the G0-phase of the cell cycle and growth recovery when cells were returned to normoxia. Induction of quiescence was associated with a decrease in the expression of c-Myc through mechanisms involving protein degradation and upregulation of p21. Inhibition of c-Myc mimicked the effects of severe hypoxia on CPC proliferation, also triggering quiescence. Surprisingly, these effects did not involve changes in p21 expression, indicating that other hypoxia-activated factors may induce p21 in CPCs. Our results suggest that hypoxic stress compromises CPC function by inducing quiescence in part through downregulation of c-Myc. In addition, we found that c-Myc is required to preserve CPC growth, suggesting that modulation of pathways downstream of it may re-activate CPC regenerative potential under ischemic conditions