Thesis Abstract

Background 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.

Patients and methods 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).

Results 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.

Conclusions Diagnosis and treatment of AHPs in Colombia have improved in recent decades. However, there are still important shortcomings to address.

Keywords
Colombia Developing countries Diagnostic errors Hematin Heme Latin America Mortality Porphyria Rare diseases

Abbreviations

AHPs       Acute hepatic porphyrias
AIP         Acute intermittent porphyria
ALA         Aminolevulinic acid
ALAS1     Aminolevulinic acid synthase 1
DNA         Deoxyribonucleic acid
GnA         Gonadorelin analogs
HCP         Hereditary coproporphyria
HMBS       Hydroxymethylbilane synthase
NAPOS     Norwegian Porphyria Centre
OLT         Orthotopic liver transplantation
PBG         Porphobilinogen
PRES       Posterior reversible encephalopathy syndrome
RNA         Ribonucleic acid
VP           Variegate porphyria

Thesis Overview