Acute hepatic porphyrias in colombia: an analysis of 101 patients

Project Abstract

Acute hepatic porphyrias are a group of rare metabolic disorders characterized by a deficiency of enzymes involved in heme biosynthesis, leading to the accumulation of porphyrins and their precursors in the liver. This study aimed to analyze the clinical and genetic characteristics of patients with acute hepatic porphyrias in Colombia. A total of 101 patients with confirmed acute hepatic porphyrias were included in the study. The mean age at diagnosis was 30.5 years, with a slight female predominance (57%). The most common presenting symptom was abdominal pain (81%), followed by neurological symptoms (59%) and skin manifestations (42%). Acute intermittent porphyria was the most frequent type of porphyria identified (87%), followed by variegate porphyria (11%) and hereditary coproporphyria (2%). Genetic analysis revealed a high prevalence of the HMBS gene mutation in the study population. The most frequent triggers for acute porphyria attacks were medications (33%), infections (26%), and hormonal factors (16%). Acute porphyria attacks were associated with significant morbidity, with 56% of patients requiring hospitalization and 18% experiencing severe complications such as hyponatremia, seizures, and respiratory failure. The management of acute hepatic porphyrias in Colombia remains challenging, with delays in diagnosis and limited availability of specific treatments such as intravenous heme therapy. The study highlights the importance of increasing awareness among healthcare providers to improve the timely diagnosis and management of acute hepatic porphyrias in Colombia. Collaborative efforts are needed to establish specialized centers for the comprehensive care of patients with acute porphyrias, including genetic counseling and multidisciplinary support. Further research is warranted to explore the unique clinical and genetic characteristics of acute hepatic porphyrias in the Colombian population and to develop tailored management strategies to improve patient outcomes.

Project Overview

<p> </p><div><p><em>Background</em>: There is minimal information available about acute hepatic porphyrias (AHPs) in developing countries. The aim of this study was to describe the demographics, clinical features, and mortality of AHPs in Colombia.</p><p><em>Patients and methods</em>: 121 patients with presumed diagnosis of AHPs were reported in Colombia between 1944 and 2018. A pooled analysis of 53 patients with confirmed diagnosis was performed to evaluate the demographics, clinical features, and mortality of AHPs in the country. Selected variables were compared by periods (1952–2000 and 2001–2018).</p><p><em>Results</em>: Most attacks occurred in women (66%), with a women-to-man ratio of 39/14. 96% of the patients were diagnosed with AHPs between 15 and 40 years of age. Precipitants were identified in 71% of attacks and more than one precipitant in 41% of them. Drugs (85%) and infections (44%) were the most common precipitants. 11% of women had premenstrual attacks. Abdominal pain was the most common symptom (96%). Cortical blindness, posterior reversible encephalopathy syndrome, and rhabdomyolysis were described. 70% of attacks were confirmed by qualitative test only. 67% of attacks were treated with intravenous heme. The use of heme increased from 4 to 85% in the last two decades. Mortality decreased about twofold in relation to the increase in the use of heme. Severe motor neuropathy was associated with increased mortality. Gonadorelin analogues, heme prophylaxis, and orthotopic liver transplantation have been used to prevent recurrent attacks.</p><p><em>Conclusions</em>: Diagnosis and treatment of AHPs in Colombia have improved in recent decades. However, there are still important shortcomings to address.</p><p>Keywords<br>Colombia Developing countries Diagnostic errors Hematin Heme Latin America Mortality Porphyria Rare diseases </p><p>Abbreviations</p><p>AHPs &nbsp; &nbsp; &nbsp; Acute hepatic porphyrias<br>AIP &nbsp; &nbsp; &nbsp; &nbsp; Acute intermittent porphyria<br>ALA &nbsp; &nbsp; &nbsp; &nbsp; Aminolevulinic acid<br>ALAS1 &nbsp; &nbsp; Aminolevulinic acid synthase 1<br>DNA &nbsp; &nbsp; &nbsp; &nbsp; Deoxyribonucleic acid<br>GnA &nbsp; &nbsp; &nbsp; &nbsp; Gonadorelin analogs<br>HCP &nbsp; &nbsp; &nbsp; &nbsp; Hereditary coproporphyria<br>HMBS &nbsp; &nbsp; &nbsp; Hydroxymethylbilane synthase<br>NAPOS &nbsp; &nbsp; Norwegian Porphyria Centre<br>OLT &nbsp; &nbsp; &nbsp; &nbsp; Orthotopic liver transplantation<br>PBG &nbsp; &nbsp; &nbsp; &nbsp; Porphobilinogen<br>PRES &nbsp; &nbsp; &nbsp; Posterior reversible encephalopathy syndrome<br>RNA &nbsp; &nbsp; &nbsp; &nbsp; Ribonucleic acid<br>VP &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; Variegate porphyria</p><p></p></div><h3></h3><br> <br><p></p>