“…A new drug therapy involving the use of a small interfering RNA (siRNA) directed against delta aminolevulinic acid synthase 1, with the aim of reducing production of delta aminolevulinic acid, is currently being investigated. 2…”
Section: Discussionmentioning
confidence: 99%
“…An overwhelming majority of porphyria cases occur in women during reproductive years, in which acute onset coincides with menses. 2 Figure 1.Heme biosynthetic pathway. Dysfunction of porphobilinogen, leads to buildup of toxins and acute intermittent porphyria (AIP).…”
Section: Introductionmentioning
confidence: 99%
“…An overwhelming majority of porphyria cases occur in women during reproductive years, in which acute onset coincides with menses. 2 Clinically, the most common symptoms of AIP are nonspecific complaints of abdominal pain and weakness. 4,5 Abdominal signs often present as diffuse cramping pain; however, due to its neurologic origin, most localizing signs, such as rebound tenderness or leukocytosis, are absent.…”
Section: Introductionmentioning
confidence: 99%
“…A more permanent solution is to undergo liver transplantation, which has been shown to be curative. 2 In the following patient, administration of Dextrose-10 (D10) was utilized, in addition to hemin infusions, to stop the progression of her disease and begin reversal of her acute condition.…”
Porphyria is a metabolic disorder caused by a mutation in the heme biosynthetic pathway, with vague symptomatology and rare prevalence. A triad of hyponatremia, intermittent seizures, and abdominal pain should raise suspicion for porphyria. The diagnosis is based on increased blood porphobilinogen levels and genetic mutations. Treatment involves Dextrose-10 administration followed by hematin infusions as soon as possible. A maintenance dose of hematin is required in some cases. Here, we report a delayed diagnosis of acute intermittent porphyria (AIP) in an 18-year-old female, who first presented with severe anemia attributed to iron deficiency from menstrual blood loss. After discharge, she was readmitted with bilateral lower extremity and abdominal pain, hyponatremia, and seizure attributed to polypharmacy. During this second hospitalization, she was transferred to our hospital complaining of chest pain, shortness of breath, markedly decreased weakness, dysphagia, and hallucinations. After an extensive workup, she was diagnosed with AIP, and Dextrose-10 and hemin infusion were started. Our patient was found to have a missense mutation in the Hydroxymethylbilane synthase gene. She recovered after an extended ICU stay of 45 days and was discharged with a moderate improvement of weakness. Early diagnosis is necessary to prevent severe manifestations and long-term sequelae, such as axonal neuropathy, which occurred in the presented case.
“…A new drug therapy involving the use of a small interfering RNA (siRNA) directed against delta aminolevulinic acid synthase 1, with the aim of reducing production of delta aminolevulinic acid, is currently being investigated. 2…”
Section: Discussionmentioning
confidence: 99%
“…An overwhelming majority of porphyria cases occur in women during reproductive years, in which acute onset coincides with menses. 2 Figure 1.Heme biosynthetic pathway. Dysfunction of porphobilinogen, leads to buildup of toxins and acute intermittent porphyria (AIP).…”
Section: Introductionmentioning
confidence: 99%
“…An overwhelming majority of porphyria cases occur in women during reproductive years, in which acute onset coincides with menses. 2 Clinically, the most common symptoms of AIP are nonspecific complaints of abdominal pain and weakness. 4,5 Abdominal signs often present as diffuse cramping pain; however, due to its neurologic origin, most localizing signs, such as rebound tenderness or leukocytosis, are absent.…”
Section: Introductionmentioning
confidence: 99%
“…A more permanent solution is to undergo liver transplantation, which has been shown to be curative. 2 In the following patient, administration of Dextrose-10 (D10) was utilized, in addition to hemin infusions, to stop the progression of her disease and begin reversal of her acute condition.…”
Porphyria is a metabolic disorder caused by a mutation in the heme biosynthetic pathway, with vague symptomatology and rare prevalence. A triad of hyponatremia, intermittent seizures, and abdominal pain should raise suspicion for porphyria. The diagnosis is based on increased blood porphobilinogen levels and genetic mutations. Treatment involves Dextrose-10 administration followed by hematin infusions as soon as possible. A maintenance dose of hematin is required in some cases. Here, we report a delayed diagnosis of acute intermittent porphyria (AIP) in an 18-year-old female, who first presented with severe anemia attributed to iron deficiency from menstrual blood loss. After discharge, she was readmitted with bilateral lower extremity and abdominal pain, hyponatremia, and seizure attributed to polypharmacy. During this second hospitalization, she was transferred to our hospital complaining of chest pain, shortness of breath, markedly decreased weakness, dysphagia, and hallucinations. After an extensive workup, she was diagnosed with AIP, and Dextrose-10 and hemin infusion were started. Our patient was found to have a missense mutation in the Hydroxymethylbilane synthase gene. She recovered after an extended ICU stay of 45 days and was discharged with a moderate improvement of weakness. Early diagnosis is necessary to prevent severe manifestations and long-term sequelae, such as axonal neuropathy, which occurred in the presented case.
“…Genetic testing, normally targeted gene sequencing, becomes critical to define the mutation(s) in a family and make genetic counseling possible. However, diagnosis of porphyrias are often overlooked due to, a large extent, the difficulty in performing the specific biochemical assays and absence of specialized porphyria centers, particularly in developing countries 20– 22 .…”
Background: Basic and clinical scientific research at the University of South Florida (USF) have intersected to support a multi-faceted approach around a common focus on rare iron-related diseases. We proposed a modified version of the National Center for Biotechnology Information’s (NCBI) Hackathon-model to take full advantage of local expertise in building “Iron Hack”, a rare disease-focused hackathon. As the collaborative, problem-solving nature of hackathons tends to attract participants of highly-diverse backgrounds, organizers facilitated a symposium on rare iron-related diseases, specifically porphyrias and Friedreich’s ataxia, pitched at general audiences.
Methods: The hackathon was structured to begin each day with presentations by expert clinicians, genetic counselors, researchers focused on molecular and cellular biology, public health/global health, genetics/genomics, computational biology, bioinformatics, biomolecular science, bioengineering, and computer science, as well as guest speakers from the American Porphyria Foundation (APF) and Friedreich’s Ataxia Research Alliance (FARA) to inform participants as to the human impact of these diseases.
Results: As a result of this hackathon, we developed resources that are relevant not only to these specific disease-models, but also to other rare diseases and general bioinformatics problems. Within two and a half days, “Iron Hack” participants successfully built collaborative projects to visualize data, build databases, improve rare disease diagnosis, and study rare-disease inheritance.
Conclusions: The purpose of this manuscript is to demonstrate the utility of a hackathon model to generate prototypes of generalizable tools for a given disease and train clinicians and data scientists to interact more effectively.
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