Scientific letter
Southeast Asian ovalocytosis
Ovalocitosis del Sudeste Asiático
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array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Rafael" "apellidos" => "del Orbe Barreto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Cruces, Barakaldo, Vizcaya, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ovalocitosis del Sudeste Asiático" ] ] "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" => 567 "Ancho" => 755 "Tamanyo" => 75337 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Peripheral blood smear (Wright's stain ×100) showing theta cells (oval in shape, with several fissures or stomata, indicated by black arrowheads), elliptocytes (green arrowheads), and stomatocytes (red arrowheads).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Southeast Asian ovalocytosis (SAO) is an autosomal dominantly inherited disorder of the red cell membrane caused by a 27-nucleotide deletion in the <span class="elsevierStyleItalic">SLC4A1 gene,</span> which triggers the loss of amino acids 400–408 of the band 3 protein. There is an isoform of the protein in the kidneys whose dysfunction leads to an inability to acidify urine, triggering distal tubular acidosis; coexistence of this entity with SAO is common in homozygous individuals.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of carriers is high in southern Thailand, Malaysia, the Philippines, Indonesia, and Papua New Guinea, affecting 5–25% of the population. SAO protects against some forms of malaria.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A literature search was carried out in PubMed for articles dated between 1990 and 2020 using the keywords: Southeast Asian ovalocytosis, SLC4A1 gene, hemoglobinopathy, distal renal tubular acidosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We report the case of a 13-year-old girl of Filipino origin, referred by paediatrics for the study of hereditary spherocytosis due to the finding of hyperchromia in routine laboratory tests. The patient had been adopted at 3 years of age, with no information on her family or neonatal history and without previous symptoms of jaundice, biliary colic, or haemolytic crisis. Physical examination was normal. The blood test showed the following results: haemoglobin 13.3<span class="elsevierStyleHsp" style=""></span>g/dl (12–16); MCV 84.6<span class="elsevierStyleHsp" style=""></span>fl (78–90); MCH 27.4<span class="elsevierStyleHsp" style=""></span>pg (26–30); MCHC 32.4<span class="elsevierStyleHsp" style=""></span>g/dl (31–34), with normal levels of WBC and platelets. Reticulocytes: 90<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">3</span>/ul (0.020−0.085). The peripheral blood smear revealed abundant stomatocytes, theta cells, isolated target cells, and elliptocytes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Erythrocyte osmotic resistance was increased in the immediate reading. The urinalysis showed no abnormalities. Glucose-6-phosphate dehydrogenase (G6PD) levels: 273<span class="elsevierStyleHsp" style=""></span>U/10<span class="elsevierStyleSup">12</span> (220–570). The study was completed with high-performance liquid chromatography and haemoglobin electrophoresis, with no abnormal haemoglobins detected. Total bilirubin: 0.66<span class="elsevierStyleHsp" style=""></span>mg/dl (0.30–1.20), direct bilirubin: 0.24<span class="elsevierStyleHsp" style=""></span>mg/dl (<0.30), LDH: 181<span class="elsevierStyleHsp" style=""></span>U/l (120–246), haptoglobin: 19<span class="elsevierStyleHsp" style=""></span>mg/dl (30–200). Given the suspicion of membranopathy, a genetic study was performed by NGS, finding a heterozygous mutation in <span class="elsevierStyleItalic">SLC4A1</span>: c.1199_1225del, SAO-causing variant, and a mutation in gene <span class="elsevierStyleItalic">G6PD</span>: c.871G>A heterozygous, with the definitive diagnosis of SAO and carrier of a pathogenic variant associated with G6PD deficiency.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">SAO is a rare entity in the Western world, and this is the first case diagnosed in Spain, to the best of our knowledge. In homozygous patients it is a life-threatening condition, resulting in death prenatally or within a few months of birth. In heterozygous patients, it is asymptomatic, without significant anaemia, and may present with self-limiting neonatal jaundice that resolves after a few years of age, data not available for our patient.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In the peripheral blood smear, it is suspected by macroovalocytes, stomatocytes and theta cells with 1–2 transverse fissures (elliptocytes-stomatocytes) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Given the low prevalence in our setting and the scarce clinical expression, the characterisation of SAO is difficult, requiring genetic methods to establish a diagnosis of certainty, as it has a nondescript clinical presentation coupled with a smear that lacks a striking increase in theta cells, which are characteristic of the condition.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Definitive diagnosis was made with genetic testing. The mutation was identified by NGS in the gene <span class="elsevierStyleItalic">SLC4A1,</span> as well as <span class="elsevierStyleItalic">G6PD gene mutation.</span> The latter is prevalent in Thailand, reaching up to 20% in some series, with the reported ‒<span class="elsevierStyleItalic">Viang-chan</span> (871G>A)‒ variant being the most common.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Expression of both mutations can lead to polymorphisms with an unusual clinical presentation and long-term complications that require careful medical evaluation and treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Given the increase in migratory flows and adoptions, it is foreseeable that more and more cases of OSA will be reported in our country, which is why it is important to be aware of this disease, as well as the need for genetic counselling in family planning.</p></span>" "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" => 567 "Ancho" => 755 "Tamanyo" => 75337 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Peripheral blood smear (Wright's stain ×100) showing theta cells (oval in shape, with several fissures or stomata, indicated by black arrowheads), elliptocytes (green arrowheads), and stomatocytes (red arrowheads).</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" => "High prevalence of Southeast Asian ovalocytosis in Malays with distal renal tubular acidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N.M. 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