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Brote agudo resuelto con givosirán" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2231 "Ancho" => 1258 "Tamanyo" => 119031 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Image showing the characteristic change in colour of three drops of urine in contact with Ehrlich's reagent after being shaken (Hoesch test).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute intermittent porphyria (AIP) is a rare hereditary genetic disorder that occurs in the form of acute attacks characterised by severe crisis of abdominal pain, neuropsychiatric alterations, and hyponatremia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Its diagnosis and treatment continue to be a challenge for clinicians.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a case of recurrent AIP treated in the acute phase with givosiran.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 36-year-old woman presented with diffuse colicky abdominal pain of 3 weeks of evolution. The patient had a history of recurrent abdominal pain that had occurred in outbreaks for the past 3 years.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The physical examination revealed hypertension (blood pressure 210/120 mmHg) and tachycardia (heart rate 110 bpm), without presenting any findings in examinations made with medical devices.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The blood analysis called attention to hyponatremia 127 mEq/l (normal range [NR]: 136–145), hypoosmolar (262 mOsm/kg; NR: 275–300), urine osmolarity 580 mOsm/kg (NR: 300–1300), and sodium 104 mEq/l (NR: 10–150). No alterations were observed in the red blood cell count, leukocyte formula, kidney or liver function.</p><p id="par0030" class="elsevierStylePara elsevierViewall">An abdominal ultrasound showed probable signs of acute cholecystitis, followed by an unremarkable laparoscopic cholecystectomy. In the postoperative period, her progress was torpid with increased abdominal pain, progressive tetraparesis (electromyogram suggestive of acute motor axonal polyneuropathy) and low level of consciousness, with respiratory difficulty that required admission to intensive care for monitoring and intubation.</p><p id="par0035" class="elsevierStylePara elsevierViewall">At this time, under suspicion of AIP, the Hoesch test was performed, and it gave a positive result (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Parenteral treatment with hemin and glucose serum was started.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnosis of AIP was confirmed by the determination of porphobilinogen (PBG), delta-aminolaevulinic acid (delta-ALA), porphyrins in blood, urine and faeces, erythrocyte porphobilinogen deaminase (PBGD) and genetic study, which showed that the patient was a heterozygous carrier of the c.652 G variant > A (p.Gly218 Arg) in the <span class="elsevierStyleItalic">HMBS</span> gene.</p><p id="par0045" class="elsevierStylePara elsevierViewall">During one month, the patient presented a total of three well-differentiated attacks after discontinuing treatment with hemin, despite control of the triggering factors and a diet rich in carbohydrates. In this context, it was decided to start with givosiran (2.5 mg/kg subcutaneously) as a therapeutic option in the acute phase of the disease, meeting the criteria for its administration. Since then, the patient has progressed favourably, and the hemin was able to be withdrawn. After a year of follow-up and monthly treatment with givosiran, there have been no new outbreaks, with complete functional recovery.</p><p id="par0050" class="elsevierStylePara elsevierViewall">AIP is a low-predominance inherited autosomal dominant disease resulting from the mutation of the gene that encodes the hydroxymethylbilane synthase or PBG deaminase enzyme.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Neuropathic abdominal pain is the most common symptom, and it can be associated with other manifestations, such as involvement of the central or autonomic nervous system and the syndrome of inappropriate antidiuretic hormone secretion. In some cases, clinical involvement can be very serious, producing respiratory and/or neurological compromise.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To diagnose an acute attack of AIP, elevated production and excretion of porphyrins and their precursors has to be determined. A screening test is performed with qualitative measurement of urinary PBG and urinary porphyrins, followed by quantitative determination of serum PBG, ALA, and porphyrins in blood and faeces. The diagnosis is confirmed by detecting decreased activity of the PBG deaminase enzyme and the genetic study.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Therapeutic strategies in AIP outbreaks are limited, based mainly on supportive treatment and hemin administration. At the same time, the triggering factors must be identified and an adequate carbohydrate intake must be established.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In cases of recurrent outbreaks, there is a therapy based on RNA interference (givosiran), with a rapid mechanism of action, which has been shown to improve symptom control and reduce the number of annual attacks, the levels of ALA and PBG in urine and the use of hemin treatment.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">After an exhaustive review of the literature (Pubmed/Medline and Science Direct databases, using the descriptive words "porphyria", "treatment" and "givosiran", since the approval of the drug in 2020 to the present), the first case is described of a patient with AIP resistant to hemin withdrawal, in which givosiran is used as an effective therapeutic alternative in the acute phase. It is therefore relevant and opens the way to the development of new studies with this treatment as a targeted therapy during outbreaks in selected patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0080" class="elsevierStylePara elsevierViewall">To write this article, the ethics committee of our hospital approved data collection, and there is signed consent from the patient.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0085" class="elsevierStylePara elsevierViewall">There was no type of funding to produce this article.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest or personal relationships that could have influenced the work presented in this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interests" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2231 "Ancho" => 1258 "Tamanyo" => 119031 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Image showing the characteristic change in colour of three drops of urine in contact with Ehrlich's reagent after being shaken (Hoesch test).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Porphyria: what is it and who should be evaluated?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Y. Edel" 1 => "R. Mamet" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5041/RMMJ.10333" "Revista" => array:4 [ "tituloSerie" => "Rambam Maimonides Med J." "fecha" => "2018" "volumen" => "9" "numero" => "2" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for the diagnosis and treatment of the acute porphyrias" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.E. Anderson" 1 => "J.R. Bloomer" 2 => "H.L. Bonkovsky" 3 => "J.P. Kushner" 4 => "C.A. Pierach" 5 => "R.J. Desnick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-142-6-200503150-00010" "Revista" => array:7 [ "tituloSerie" => "Ann Intern Med." 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Journal Information
Vol. 161. Issue 10.
Pages 454-455 (November 2023)
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Vol. 161. Issue 10.
Pages 454-455 (November 2023)
Letter to the Editor
Acute intermittent porphyria: acute flare-up resolved with givosiran
Porfiria aguda intermitente. Brote agudo resuelto con givosirán
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