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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The pulse oximeter&#44; a non-invasive method of measuring oxygen transported by hemoglobin inside the blood vessels&#44; is one of the most widely used devices in medical practice&#46; It emits light with 2 wavelengths of 660&#8239;nm &#40;red&#41; and 940&#8239;nm &#40;infrared&#41; that are characteristic of oxyhemoglobin and reduced hemoglobin&#44; respectively&#44; and calculates the percentage of oxyhemoglobins by comparing the absorption of light during the pulsatile wave with the baseline level&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Correlation between oxygen saturation and the partial pressure of oxygen in arterial blood is determined by the oxyhemoglobin dissociation curve&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In clinical practice&#44; a level of oxygen saturation well below the expected limits<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> means that many etiologies must be ruled out&#44; some of which are quite rare&#46; We report a case of hemoglobinopathy with altered oxygen affinity detected by pulse oximetry&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient was a 53-year-old man&#44; farmer by profession&#44; and former smoker who had started smoking at the age of 13&#44; and had quit 10 years previously&#59; pack-year index&#58; 15&#59; allergic to penicillins and intolerant to tramadol&#59; congenital ventricular septal defect&#44; with no current impact on health&#46; Family disease history included mother with chronic heart disease and father who died of non-Hodgkin&#8217;s lymphoma&#46; He has a healthy sister&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">He was referred to our clinic from primary care for a 6-month history of dyspnea on intense exertion&#44; and no other respiratory symptoms&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Physical examination showed no relevant findings&#44; no cyanosis&#44; no tachypnea&#44; no other signs of chronic respiratory failure&#44; but basal oxygen saturation was 76&#37;&#8211;77&#37;&#44; surprisingly low and surprisingly well tolerated&#44; confirmed by different devices&#46; Blood gas analysis was carried out in which partial pressure of oxygen in arterial blood was below normal&#44; confirming hypoxemia with oxygen saturation of 76&#37;&#44; with a partial pressure of oxygen in arterial blood of 41&#8239;mmHg&#46; Chest radiograph was normal&#46; Spirometry was also performed&#44; and values were normal in all cases &#40;FVC&#58; 5580&#8211;117&#37;&#44; FEV1&#58; 4470&#8211;123&#37;&#44; FEV1&#47;FVC&#58; 80&#37;&#44; MEF&#58; 25&#8211;75&#37;&#58; 3340&#8211;100&#37;&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To rule out the most common causes of hypoxemia&#44; we performed a computed tomography of the chest which showed only a persistent left superior vena cava&#44; and hypoplastic brachiocephalic trunk&#44; thus excluding&#44; among other problems&#44; thromboembolic disease at a radiological level&#46; Diffusion testing was also performed&#44; which was normal&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the patient&#8217;s cardiological history&#44; we requested a specific reassessment to rule out any kind of anteriovenous shunt&#58; transthoracic and transesophageal echocardiograms and a bubble study were performed&#44; ruling out any active ventricular septal defect&#46; Cardiac catheterization was also performed&#44; showing normal left ventricular ejection fraction&#44; and ruling out changes in coronary artery lumens and in the pulmonary and systemic circulation&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical laboratory tests were performed&#44; including full blood count&#44; biochemistry&#44; kidney function&#44; liver profile&#44; thyroid markers&#44; etc&#46;&#41;&#44; showing no changes&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; after contacting the hematology department&#44; we performed hemoglobin electrophoresis&#58; the patient had hemoglobin with abnormal electrophoretic mobility of up to 35&#37;&#46; P50 was also calculated&#44; which in our patient was 34&#46;5&#44; consistent with hemoglobinopathy with altered oxygen affinity&#46; Given this suspicion&#44; we requested the Hospital San Carlos in Madrid to identify the anomalous hemoglobin&#46; After DNA sequencing&#44; the patient was determined to have hemoglobin Rothschild&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The DNA study identified the TGG&#8239;&#62;&#8239;CGG mutation at codon 37 in the 2nd exon of the gene &#946; in the allele that determines the replacement of amino acid tryptophan by arginine at position 3 of the C helix of the chain &#946; encoded by the mutated allele&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">High performance liquid chromatography was also performed&#44; which showed abnormal hemoglobin in the fraction corresponding to hemoglobin D&#59; after new sampling for arterial &#40;p50 value of 34&#46;5&#41; and venous blood gases&#44; we concluded that this was hemoglobin Rothschild &#91;&#946;37 &#40;C3&#41; Asp&#8239;&#62;&#8239;Tyr&#59; HBB&#58; c&#46;112&#8239;T&#8239;&#62;&#8239;C&#93; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Hemoglobin consists of a tetramer of polypeptide chains of globins&#44; a pair of &#945; chains&#44; 141 amino acids in length&#44; and a pair of &#946; chains of 146 amino acids&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The main hemoglobin in adults is HbA&#44; which has an &#945;2&#946;2 structure&#46; Each heme fraction can bind to a single molecule of oxygen&#44; so that each molecule can carry up to 4 molecules of oxygen&#46; The key properties that are altered in hemoglobin diseases are solubility and the reversible union of oxygen&#44; which depends particularly on hydrophilic amino acids&#44; hydrophobic amino acids that line the heme pocket&#44; a histidine in the F helix&#44; and the amino acids that form the contact surfaces of &#945;1&#946;1 and &#945;1&#946;2&#46; The alteration that modifies oxygen affinity is located in these regions&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Hemoglobin Rothschild is a mutation of the hemoglobin&#946; chain&#44; where it substitutes the tryptophan residue at position &#946;37&#40;C3&#41; with arginine&#46; Tryptophan in B37 &#40;C3&#41; is a contact point at the &#945;1&#946;2 and &#945;2&#946;1 interfaces&#44; and the replacement of tryptophan by arginine leads to destabilization of the interfaces affected during oxygenation and deoxygenation&#58; a deviation from normal oxygen levels is expected&#44; but this deviation occurs only at the molecular level and has no apparent clinical manifestation in patients&#44; who usually remain asymptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> It should be noted that the partial pressure at which the hemoglobin is half saturated is p50&#44; HbA has a p50 of 25&#8239;&#177;&#8239;2&#8239;mmHg&#44; whereas hemoglobin Rothschild &#91;&#946; 37&#40;C3&#41; RTP&#8239;&#8594;&#8239;Erg&#93; has a higher p50 due to its low affinity to oxygen&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Altered oxygen saturation in our patient&#44; determined by pulse oximeter&#44; was the initial reason for performing this study&#46; After identifying the cause of the problem to be hemoglobinopathy and explaining to the patient the limited clinical implications of this finding&#44; he was able to minimize his problems and symptoms&#44; which had been exaggerated by his knowledge of the abnormality and his fear of possible disease&#46; We believe that&#44; in patients presenting low oxygen saturations with no obvious cause and little clinical concordance&#44; this type of hemoglobinopathy should be taken into consideration because despite its rarity&#44; it can appear in routine practice&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In addition&#44; to complete the family study and to identify other cases&#44; pulse oximetry was used to identify our patient&#39;s sister and 2 nephews as carriers&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">When a patient presents with low oxygen saturations with no apparent pathological cause to explain the hypoxia&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;7</span></a> we must bear in mind an oxygen affinity alteration<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a> of hemoglobin&#44; since many of these conditions develop without symptoms<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and uncommon diseases can be detected by measuring saturation using a pulse oximeter&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> as in the case which we report here&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gonz&#225;lez Garc&#237;a LM&#44; et al&#46; Una causa infrecuente de saturaci&#243;n arterial de ox&#237;geno baja&#58; hemoglobinopat&#237;a de Rothschild&#46; Arch Bronconeumol&#46; 2019&#59;55&#58;657&#8211;659&#46;</p>"
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Scientific Letter
Hemoglobin Rothschild: A rare cause of low arterial oxygen saturation
Una causa infrecuente de saturación arterial de oxígeno baja: hemoglobinopatía de Rothschild
Luis Manuel González Garcíaa, José María Hernández Pérezb,
Corresponding author
jmherper@hotmail.com

Corresponding author.
, María Tapia Torresc, Paloma Ropero Gradillad
a Centro de Salud de Breña Baja, Área de Salud de La Isla de La Palma, Breña Baja, Santa Cruz de Tenerife, Spain
b Sección de Neumología, Hospital General de La Palma, Breña Alta, La Palma, Santa Cruz de Tenerife, Spain
c Servicio de Hematología, Hospital General de La Palma, Breña Alta, La Palma, Santa Cruz de Tenerife, Spain
d Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The pulse oximeter&#44; a non-invasive method of measuring oxygen transported by hemoglobin inside the blood vessels&#44; is one of the most widely used devices in medical practice&#46; It emits light with 2 wavelengths of 660&#8239;nm &#40;red&#41; and 940&#8239;nm &#40;infrared&#41; that are characteristic of oxyhemoglobin and reduced hemoglobin&#44; respectively&#44; and calculates the percentage of oxyhemoglobins by comparing the absorption of light during the pulsatile wave with the baseline level&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Correlation between oxygen saturation and the partial pressure of oxygen in arterial blood is determined by the oxyhemoglobin dissociation curve&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In clinical practice&#44; a level of oxygen saturation well below the expected limits<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> means that many etiologies must be ruled out&#44; some of which are quite rare&#46; We report a case of hemoglobinopathy with altered oxygen affinity detected by pulse oximetry&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient was a 53-year-old man&#44; farmer by profession&#44; and former smoker who had started smoking at the age of 13&#44; and had quit 10 years previously&#59; pack-year index&#58; 15&#59; allergic to penicillins and intolerant to tramadol&#59; congenital ventricular septal defect&#44; with no current impact on health&#46; Family disease history included mother with chronic heart disease and father who died of non-Hodgkin&#8217;s lymphoma&#46; He has a healthy sister&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">He was referred to our clinic from primary care for a 6-month history of dyspnea on intense exertion&#44; and no other respiratory symptoms&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Physical examination showed no relevant findings&#44; no cyanosis&#44; no tachypnea&#44; no other signs of chronic respiratory failure&#44; but basal oxygen saturation was 76&#37;&#8211;77&#37;&#44; surprisingly low and surprisingly well tolerated&#44; confirmed by different devices&#46; Blood gas analysis was carried out in which partial pressure of oxygen in arterial blood was below normal&#44; confirming hypoxemia with oxygen saturation of 76&#37;&#44; with a partial pressure of oxygen in arterial blood of 41&#8239;mmHg&#46; Chest radiograph was normal&#46; Spirometry was also performed&#44; and values were normal in all cases &#40;FVC&#58; 5580&#8211;117&#37;&#44; FEV1&#58; 4470&#8211;123&#37;&#44; FEV1&#47;FVC&#58; 80&#37;&#44; MEF&#58; 25&#8211;75&#37;&#58; 3340&#8211;100&#37;&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To rule out the most common causes of hypoxemia&#44; we performed a computed tomography of the chest which showed only a persistent left superior vena cava&#44; and hypoplastic brachiocephalic trunk&#44; thus excluding&#44; among other problems&#44; thromboembolic disease at a radiological level&#46; Diffusion testing was also performed&#44; which was normal&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the patient&#8217;s cardiological history&#44; we requested a specific reassessment to rule out any kind of anteriovenous shunt&#58; transthoracic and transesophageal echocardiograms and a bubble study were performed&#44; ruling out any active ventricular septal defect&#46; Cardiac catheterization was also performed&#44; showing normal left ventricular ejection fraction&#44; and ruling out changes in coronary artery lumens and in the pulmonary and systemic circulation&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical laboratory tests were performed&#44; including full blood count&#44; biochemistry&#44; kidney function&#44; liver profile&#44; thyroid markers&#44; etc&#46;&#41;&#44; showing no changes&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; after contacting the hematology department&#44; we performed hemoglobin electrophoresis&#58; the patient had hemoglobin with abnormal electrophoretic mobility of up to 35&#37;&#46; P50 was also calculated&#44; which in our patient was 34&#46;5&#44; consistent with hemoglobinopathy with altered oxygen affinity&#46; Given this suspicion&#44; we requested the Hospital San Carlos in Madrid to identify the anomalous hemoglobin&#46; After DNA sequencing&#44; the patient was determined to have hemoglobin Rothschild&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The DNA study identified the TGG&#8239;&#62;&#8239;CGG mutation at codon 37 in the 2nd exon of the gene &#946; in the allele that determines the replacement of amino acid tryptophan by arginine at position 3 of the C helix of the chain &#946; encoded by the mutated allele&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">High performance liquid chromatography was also performed&#44; which showed abnormal hemoglobin in the fraction corresponding to hemoglobin D&#59; after new sampling for arterial &#40;p50 value of 34&#46;5&#41; and venous blood gases&#44; we concluded that this was hemoglobin Rothschild &#91;&#946;37 &#40;C3&#41; Asp&#8239;&#62;&#8239;Tyr&#59; HBB&#58; c&#46;112&#8239;T&#8239;&#62;&#8239;C&#93; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Hemoglobin consists of a tetramer of polypeptide chains of globins&#44; a pair of &#945; chains&#44; 141 amino acids in length&#44; and a pair of &#946; chains of 146 amino acids&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The main hemoglobin in adults is HbA&#44; which has an &#945;2&#946;2 structure&#46; Each heme fraction can bind to a single molecule of oxygen&#44; so that each molecule can carry up to 4 molecules of oxygen&#46; The key properties that are altered in hemoglobin diseases are solubility and the reversible union of oxygen&#44; which depends particularly on hydrophilic amino acids&#44; hydrophobic amino acids that line the heme pocket&#44; a histidine in the F helix&#44; and the amino acids that form the contact surfaces of &#945;1&#946;1 and &#945;1&#946;2&#46; The alteration that modifies oxygen affinity is located in these regions&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Hemoglobin Rothschild is a mutation of the hemoglobin&#946; chain&#44; where it substitutes the tryptophan residue at position &#946;37&#40;C3&#41; with arginine&#46; Tryptophan in B37 &#40;C3&#41; is a contact point at the &#945;1&#946;2 and &#945;2&#946;1 interfaces&#44; and the replacement of tryptophan by arginine leads to destabilization of the interfaces affected during oxygenation and deoxygenation&#58; a deviation from normal oxygen levels is expected&#44; but this deviation occurs only at the molecular level and has no apparent clinical manifestation in patients&#44; who usually remain asymptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> It should be noted that the partial pressure at which the hemoglobin is half saturated is p50&#44; HbA has a p50 of 25&#8239;&#177;&#8239;2&#8239;mmHg&#44; whereas hemoglobin Rothschild &#91;&#946; 37&#40;C3&#41; RTP&#8239;&#8594;&#8239;Erg&#93; has a higher p50 due to its low affinity to oxygen&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Altered oxygen saturation in our patient&#44; determined by pulse oximeter&#44; was the initial reason for performing this study&#46; After identifying the cause of the problem to be hemoglobinopathy and explaining to the patient the limited clinical implications of this finding&#44; he was able to minimize his problems and symptoms&#44; which had been exaggerated by his knowledge of the abnormality and his fear of possible disease&#46; We believe that&#44; in patients presenting low oxygen saturations with no obvious cause and little clinical concordance&#44; this type of hemoglobinopathy should be taken into consideration because despite its rarity&#44; it can appear in routine practice&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In addition&#44; to complete the family study and to identify other cases&#44; pulse oximetry was used to identify our patient&#39;s sister and 2 nephews as carriers&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">When a patient presents with low oxygen saturations with no apparent pathological cause to explain the hypoxia&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;7</span></a> we must bear in mind an oxygen affinity alteration<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a> of hemoglobin&#44; since many of these conditions develop without symptoms<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and uncommon diseases can be detected by measuring saturation using a pulse oximeter&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> as in the case which we report here&#46;</p></span>"
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Article information
ISSN: 15792129
Original language: English
DOI:10.1016/j.arbr.2019.05.013
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