Letter to the Editor
Methylmalonic acidemia with emergency hypertension
Acidemia metilmalónica con hipertensión de emergencia
Bahareh Yaghmaeia, Parastoo Rostamia,
, Farnaz Najmi Varzanehb,c, Behdad Ghariba, Behnaz Bazargania, Nima Rezaeib,c,d
Autor para correspondencia
a Department of Pediatrics, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
b Research Center for Immunodeficiencies, Children's Medical Center, Tehran, Iran
c Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
d Universal Scientific Education and Research Network (USERN), Tehran, Iran
Leído
9718
Vecesse ha leído el artículo
2802
Total PDF
6916
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S0211699515001381" "issn" => "02116995" "doi" => "10.1016/j.nefro.2015.08.003" "estado" => "S300" "fechaPublicacion" => "2016-01-01" "aid" => "86" "copyright" => "Sociedad Española de Nefrología" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Nefrologia. 2016;36:75-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5482 "formatos" => array:3 [ "EPUB" => 387 "HTML" => 4255 "PDF" => 840 ] ] "itemSiguiente" => array:20 [ "pii" => "S0211699515001939" "issn" => "02116995" "doi" => "10.1016/j.nefro.2015.10.008" "estado" => "S300" "fechaPublicacion" => "2016-01-01" "aid" => "126" "copyright" => "Sociedad Española de Nefrología" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Nefrologia. 2016;36:76-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 11007 "formatos" => array:3 [ "EPUB" => 327 "HTML" => 9791 "PDF" => 889 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Glomerulonefritis necrosante en el síndrome por consumo de cocaína y levamisol" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "76" "paginaFinal" => "78" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Necrotising glomerulonephritis in levamisole-contaminated cocaine use" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 703 "Ancho" => 975 "Tamanyo" => 240970 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Glomérulo con necrosis fibrinoide segmentaria y semiluna fibrosa (PAS<span class="elsevierStyleHsp" style=""></span>×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Esther Sirvent, Ricardo Enríquez, Encarnación Andrada, María Sánchez, Isabel Millán, César González" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ana Esther" "apellidos" => "Sirvent" ] 1 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Enríquez" ] 2 => array:2 [ "nombre" => "Encarnación" "apellidos" => "Andrada" ] 3 => array:2 [ "nombre" => "María" "apellidos" => "Sánchez" ] 4 => array:2 [ "nombre" => "Isabel" "apellidos" => "Millán" ] 5 => array:2 [ "nombre" => "César" "apellidos" => "González" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S201325141600033X" "doi" => "10.1016/j.nefroe.2016.03.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S201325141600033X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699515001939?idApp=UINPBA000064" "url" => "/02116995/0000003600000001/v1_201602110042/S0211699515001939/v1_201602110042/es/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0211699515001538" "issn" => "02116995" "doi" => "10.1016/j.nefro.2015.07.007" "estado" => "S300" "fechaPublicacion" => "2016-01-01" "aid" => "101" "copyright" => "Sociedad Española de Nefrología" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Nefrologia. 2016;36:72-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5671 "formatos" => array:3 [ "EPUB" => 305 "HTML" => 4601 "PDF" => 765 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Eculizumab for the treatment of an atypical hemolytic uremic syndrome with mutations in complement factor I and C3" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "72" "paginaFinal" => "75" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eculizumab para el tratamiento de un síndrome urémico hemolítico atípico con mutaciones en los factores I y C3 del sistema del complemento" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3462 "Ancho" => 2454 "Tamanyo" => 392693 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical course: laboratory data and treatment. Corticosteroid therapy was started with intravenous administration of methylprednisolone (1000<span class="elsevierStyleHsp" style=""></span>mg/day for 3 days) followed by oral prednisolone and an initial dosage of 60<span class="elsevierStyleHsp" style=""></span>mg/day. This dosage was maintained until the 53rd day after admission, with posterior tapering. Rituximab (arrows) was administered at a dose of 600<span class="elsevierStyleHsp" style=""></span>mg (375<span class="elsevierStyleHsp" style=""></span>mg/m2) on the 27th, 34th, 41st and 48th days after admission. Cyclophosphamide (arrowhead) was administered in a single dose of 1000<span class="elsevierStyleHsp" style=""></span>mg on the 61st day after admission (2nd day after readmission). Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg for a week for 4 weeks, started on the 158th day after admission, followed by a dosage of 1200<span class="elsevierStyleHsp" style=""></span>mg 1 week later an then a maintenance dose of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks. This dosage is still being continued. We performed a total of 79 plasma exchange sessions. The last three laboratorial test results were done on the 270th, 340th and 466th days following first admission.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Emanuel Ferreira, Nuno Oliveira, Maria Marques, Luís Francisco, Ana Santos, Armando Carreira, Mário Campos" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Emanuel" "apellidos" => "Ferreira" ] 1 => array:2 [ "nombre" => "Nuno" "apellidos" => "Oliveira" ] 2 => array:2 [ "nombre" => "Maria" "apellidos" => "Marques" ] 3 => array:2 [ "nombre" => "Luís" "apellidos" => "Francisco" ] 4 => array:2 [ "nombre" => "Ana" "apellidos" => "Santos" ] 5 => array:2 [ "nombre" => "Armando" "apellidos" => "Carreira" ] 6 => array:2 [ "nombre" => "Mário" "apellidos" => "Campos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699515001538?idApp=UINPBA000064" "url" => "/02116995/0000003600000001/v1_201602110042/S0211699515001538/v1_201602110042/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Methylmalonic acidemia with emergency hypertension" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "75" "paginaFinal" => "76" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Bahareh Yaghmaei, Parastoo Rostami, Farnaz Najmi Varzaneh, Behdad Gharib, Behnaz Bazargani, Nima Rezaei" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Bahareh" "apellidos" => "Yaghmaei" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Parastoo" "apellidos" => "Rostami" "email" => array:1 [ 0 => "drp_rostami@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Farnaz Najmi" "apellidos" => "Varzaneh" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Behdad" "apellidos" => "Gharib" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Behnaz" "apellidos" => "Bazargani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Nima" "apellidos" => "Rezaei" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Research Center for Immunodeficiencies, Children's Medical Center, Tehran, Iran" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Universal Scientific Education and Research Network (USERN), Tehran, Iran" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Acidemia metilmalónica con hipertensión de emergencia" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Methylmalonic acidemia (MMA) is a heterogeneous disorder of propionate metabolism. MMA is caused by deficiency of the mitochondrial enzyme, methylmalonyl-CoA mutase-apoenzyme activity (MUT) or defective in adenosylcobalamin (coenzyme) synthesis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> The most patients with cblA and half patients with cblB forms of MMA are responsive to vitamin B12.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3</span></a> Clinical manifestation of MMA may be acute or chronic. The acute form of the disease occurs during infancy and even as early as the second day of life with poor feeding, vomiting, dehydration, weight loss, temperature instability, lethargy, hypotonia, seizure and progressing to coma. Laboratory findings include: metabolic acidosis, ketosis, hypoglycemia, hyperlactatemia, hyperammonemia, pancytopenia.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Definitive diagnosis of isolated MMA is based on analysis of organic acids in plasma and/or urine; however genetic testing diagnosis in some condition is accessible to confirm the diagnosis of isolated MMA. Below, we describe the presentation and management of two cases of MMA with severe hypertention.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first case was a 46-day-old girl, admitted to the emergency department because of generalized edema and severe hypertension. She was born from consanguineous parents at term with a birth weight 2.600<span class="elsevierStyleHsp" style=""></span>kg. She had frequent vomiting in 9th day of life. Edema of hands and feet appeared in 39th day of life. On admission, she had SBP 130<span class="elsevierStyleHsp" style=""></span>mmHg (above 99th), DBP 75<span class="elsevierStyleHsp" style=""></span>mmHg (above 99th), periorbital and legs pitting edema and respiratory distress. Laboratory findings included: microscopic hematuria, massive proteinuria, hypoalbominemia, pancytopenia and high anion gap metabolic acidosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was managed by nephrologists with diagnosis of congenital nephrotic syndrome. Angiography of abdominal aorta and renal artery were normal. She had brain atrophy and supra and infra tentorial ventricolomegaly in brain CT scan and left ventricular hypertrophy in echocardiography. Abdominal sonography was normal but both kidneys were seen larger than normal. Bone marrow aspiration (BMA) was performed because of pancytopenia which was normal. Patient's hypertension did not respond to Losartan, Hydralazine, Captopril and Amlodipine. Metabolic consulting and then metabolic tests due to refractory metabolic acidosis was done. The patient with suspected organic aciduria was treated with hydroxycobalamin 1<span class="elsevierStyleHsp" style=""></span>mg daily, biotin 10<span class="elsevierStyleHsp" style=""></span>mg daily and <span class="elsevierStyleSmallCaps">l</span>-carnitine 50<span class="elsevierStyleHsp" style=""></span>mg/kg/day. She had high level of glycine in blood amino acid chromatography but ammonia, lactate, serum B12 and hemocystein were normal. Methylmalonic aciduria confirmed with high level of urine methlmalonic acid and increased serum level of propionyl carnitine. We have increased the dose of B12 up to 2<span class="elsevierStyleHsp" style=""></span>mg IM daily but unfortunately, the patient died.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The second case was a 45-day-old boy admitted from the emergency ward with complaints of anemia, respiratory distress and severe hypertension. He was born from non-consanguineous parents at term with a birth weight 2.800<span class="elsevierStyleHsp" style=""></span>kg. The first baby of the family had died at the age of 5-months due to propionic aciduria. On examination he had respiratory distress (RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>67), SBP 134<span class="elsevierStyleHsp" style=""></span>mmHg (above 99th) and DBP 78<span class="elsevierStyleHsp" style=""></span>mmHg (above 99th) and mild pitting edema in legs. Laboratory results included: high anion gap metabolic acidosis, pancytopenia, hypoalbominemia, proteinuria, and microscopic hematuria. Lactate, ammonia, serum B12, serum hemocystein and other electrolytes were normal but serum glycine was increased. Renal artery disorder has been excluded by Doppler sonography. Abdominal sonography was normal but both kidneys had upper normal size and increased cortical echogenicity. BMA was performed because of pancytopenia which was normal. According to the familial history and our previous case, after sending samples for urine organic acid, acylcarnitine profile and chromatography of serum amino acid, B12 2<span class="elsevierStyleHsp" style=""></span>mg IM daily, carnitine 50<span class="elsevierStyleHsp" style=""></span>mg/kg/day, biotin 10<span class="elsevierStyleHsp" style=""></span>mg daily and low protein diet was started for the patient. His blood pressure was refractory to all of anti-hypertensive drugs such as Hydralazine, Captopril, Labetalol. Methylmalonic aciduria confirmed by increased of urine methylmalonic acid and serum propionyl carnitine. Despite early treatment of methylmalonic acid even without waiting for tests result, the patient died.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Chronic renal disease is a life-threatening complication of MMA and finally leads to dialysis or kidney transplantation. Renal impairment most occurs in patients with mut (0) and cblB mutation.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> The mechanism of renal injury in MMA is still unknown. Proximal tubular disorder is a main pathogenic mechanism of MMA-associated kidney disease.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> A recent case study has reported 2 cases of MMA associated with hemolytic uremic syndrome (HUS) association which revealed that probable pathogenesis of thrombotic microangiopathy could be related to the increase of plasma methylmalonic acid and homocysteine levels.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the current study, the two mentioned patients had MMA that confirmed with assessment of urine organic acid and acylcarnitine profile. They had just renal involvement that their symptom and signs were started during infancy that was refractory to all of the treatment and despite early treatment in the one of them, they died.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In summary, in each case with hematuria, proteinuria, nephrotic syndrome, unexplained hypertension or renal failure of unknown origin especially in pediatric patients, metabolic screening and urinary organic acid analysis should be carried out as soon as possible.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic renal failure in methylmalonic acidaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.H. Walter" 1 => "A. Michalski" 2 => "W.M. Wilson" 3 => "J.V. Leonard" 4 => "T.M. Barratt" 5 => "M.J. Dillon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "1989" "volumen" => "148" "paginaInicial" => "344" "paginaFinal" => "348" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2707280" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of the inherited methylmalonic acidemias" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.M. Matsui" 1 => "M.J. Mahoney" 2 => "L.E. Rosenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198304143081501" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1983" "volumen" => "308" "paginaInicial" => "857" "paginaFinal" => "861" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6132336" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neurological outcome of methylmalonic acidaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Nicolaides" 1 => "J. Leonard" 2 => "R. Surtees" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "1998" "volumen" => "78" "paginaInicial" => "508" "paginaFinal" => "512" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9713004" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Baumgartner" 1 => "F. Horster" 2 => "C. Dionisi-Vici" 3 => "G. Haliloglu" 4 => "D. Karall" 5 => "K.A. Chapman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13023-014-0130-8" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "130" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25205257" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Horster" 1 => "M.R. Baumgartner" 2 => "C. Viardot" 3 => "T. Suormala" 4 => "P. Burgard" 5 => "B. Fowler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/PDR.0b013e3180a0325f" "Revista" => array:6 [ "tituloSerie" => "Pediatr Res" "fecha" => "2007" "volumen" => "62" "paginaInicial" => "225" "paginaFinal" => "230" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17597648" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Manoli" 1 => "J.R. Sysol" 2 => "L. Li" 3 => "P. Houillier" 4 => "C. Garone" 5 => "C. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1302764110" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2013" "volumen" => "110" "paginaInicial" => "13552" "paginaFinal" => "13557" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23898205" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methylmalonic acidemia with homocystinuria. A very rare cause of kidney failure in the neonatal period" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "O. Mesa-Medina" 1 => "M. Ruiz-Pons" 2 => "V. Garcia-Nieto" 3 => "J. Leon-Gonzalez" 4 => "S. Lopez-Mendoza" 5 => "C. Solis-Reyes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3265/Nefrologia.pre2014.May.12058" "Revista" => array:6 [ "tituloSerie" => "Nefrologia" "fecha" => "2014" "volumen" => "34" "paginaInicial" => "539" "paginaFinal" => "540" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25036075" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02116995/0000003600000001/v1_201602110042/S0211699515001381/v1_201602110042/en/main.assets" "Apartado" => array:4 [ "identificador" => "48186" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas al Director" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/02116995/0000003600000001/v1_201602110042/S0211699515001381/v1_201602110042/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699515001381?idApp=UINPBA000064" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 9 | 11 | 20 |
| 2024 Octubre | 63 | 48 | 111 |
| 2024 Septiembre | 70 | 26 | 96 |
| 2024 Agosto | 77 | 59 | 136 |
| 2024 Julio | 56 | 27 | 83 |
| 2024 Junio | 49 | 42 | 91 |
| 2024 Mayo | 48 | 39 | 87 |
| 2024 Abril | 71 | 41 | 112 |
| 2024 Marzo | 35 | 24 | 59 |
| 2024 Febrero | 44 | 37 | 81 |
| 2024 Enero | 58 | 31 | 89 |
| 2023 Diciembre | 41 | 31 | 72 |
| 2023 Noviembre | 48 | 26 | 74 |
| 2023 Octubre | 74 | 43 | 117 |
| 2023 Septiembre | 41 | 27 | 68 |
| 2023 Agosto | 49 | 30 | 79 |
| 2023 Julio | 43 | 22 | 65 |
| 2023 Junio | 46 | 23 | 69 |
| 2023 Mayo | 66 | 33 | 99 |
| 2023 Abril | 33 | 14 | 47 |
| 2023 Marzo | 62 | 28 | 90 |
| 2023 Febrero | 40 | 42 | 82 |
| 2023 Enero | 33 | 20 | 53 |
| 2022 Diciembre | 93 | 36 | 129 |
| 2022 Noviembre | 53 | 28 | 81 |
| 2022 Octubre | 61 | 54 | 115 |
| 2022 Septiembre | 30 | 37 | 67 |
| 2022 Agosto | 51 | 47 | 98 |
| 2022 Julio | 35 | 49 | 84 |
| 2022 Junio | 36 | 34 | 70 |
| 2022 Mayo | 33 | 47 | 80 |
| 2022 Abril | 43 | 64 | 107 |
| 2022 Marzo | 50 | 66 | 116 |
| 2022 Febrero | 33 | 48 | 81 |
| 2022 Enero | 34 | 37 | 71 |
| 2021 Diciembre | 33 | 41 | 74 |
| 2021 Noviembre | 39 | 42 | 81 |
| 2021 Octubre | 57 | 55 | 112 |
| 2021 Septiembre | 36 | 31 | 67 |
| 2021 Agosto | 26 | 47 | 73 |
| 2021 Julio | 43 | 36 | 79 |
| 2021 Junio | 28 | 30 | 58 |
| 2021 Mayo | 40 | 34 | 74 |
| 2021 Abril | 78 | 82 | 160 |
| 2021 Marzo | 67 | 33 | 100 |
| 2021 Febrero | 77 | 22 | 99 |
| 2021 Enero | 45 | 22 | 67 |
| 2020 Diciembre | 51 | 20 | 71 |
| 2020 Noviembre | 40 | 23 | 63 |
| 2020 Octubre | 26 | 28 | 54 |
| 2020 Septiembre | 37 | 26 | 63 |
| 2020 Agosto | 46 | 17 | 63 |
| 2020 Julio | 27 | 17 | 44 |
| 2020 Junio | 36 | 20 | 56 |
| 2020 Mayo | 49 | 13 | 62 |
| 2020 Abril | 28 | 25 | 53 |
| 2020 Marzo | 33 | 19 | 52 |
| 2020 Febrero | 35 | 21 | 56 |
| 2020 Enero | 38 | 20 | 58 |
| 2019 Diciembre | 45 | 26 | 71 |
| 2019 Noviembre | 36 | 30 | 66 |
| 2019 Octubre | 28 | 11 | 39 |
| 2019 Septiembre | 29 | 21 | 50 |
| 2019 Agosto | 26 | 32 | 58 |
| 2019 Julio | 25 | 21 | 46 |
| 2019 Junio | 25 | 21 | 46 |
| 2019 Mayo | 27 | 20 | 47 |
| 2019 Abril | 66 | 31 | 97 |
| 2019 Marzo | 43 | 23 | 66 |
| 2019 Febrero | 39 | 25 | 64 |
| 2019 Enero | 29 | 17 | 46 |
| 2018 Diciembre | 144 | 47 | 191 |
| 2018 Noviembre | 223 | 32 | 255 |
| 2018 Octubre | 221 | 23 | 244 |
| 2018 Septiembre | 128 | 20 | 148 |
| 2018 Agosto | 103 | 11 | 114 |
| 2018 Julio | 91 | 16 | 107 |
| 2018 Junio | 91 | 18 | 109 |
| 2018 Mayo | 111 | 15 | 126 |
| 2018 Abril | 106 | 10 | 116 |
| 2018 Marzo | 90 | 15 | 105 |
| 2018 Febrero | 52 | 12 | 64 |
| 2018 Enero | 54 | 7 | 61 |
| 2017 Diciembre | 83 | 9 | 92 |
| 2017 Noviembre | 57 | 8 | 65 |
| 2017 Octubre | 73 | 9 | 82 |
| 2017 Septiembre | 49 | 38 | 87 |
| 2017 Agosto | 52 | 19 | 71 |
| 2017 Julio | 66 | 24 | 90 |
| 2017 Junio | 60 | 22 | 82 |
| 2017 Mayo | 71 | 21 | 92 |
| 2017 Abril | 77 | 23 | 100 |
| 2017 Marzo | 74 | 32 | 106 |
| 2017 Febrero | 43 | 12 | 55 |
| 2017 Enero | 35 | 13 | 48 |
| 2016 Diciembre | 64 | 10 | 74 |
| 2016 Noviembre | 91 | 21 | 112 |
| 2016 Octubre | 108 | 9 | 117 |
| 2016 Septiembre | 129 | 13 | 142 |
| 2016 Agosto | 129 | 5 | 134 |
| 2016 Julio | 169 | 15 | 184 |
| 2016 Junio | 127 | 0 | 127 |
| 2016 Mayo | 169 | 0 | 169 |
| 2016 Abril | 143 | 0 | 143 |
| 2016 Marzo | 168 | 0 | 168 |
| 2016 Febrero | 169 | 0 | 169 |
| 2016 Enero | 63 | 0 | 63 |
| 2015 Diciembre | 38 | 0 | 38 |
| 2015 Noviembre | 52 | 0 | 52 |
| 2015 Octubre | 2 | 0 | 2 |
Mostrar todo
