Sjogren’s syndrome presenting as hypokalemic periodic paralysis, a rare manifestation: A case series

Sjogren’s syndrome is a chronic and slowly progressing autoimmune disease characterized by lyphocytic infiltration of exocrine glands resulting in Sicca syndrome (xerostomia and keratocunjuntivitis sicca). The disease can present alone or along with other autoimmune diseases leading to significant organ specific and systemic disease. Middle aged women (Female: Male: 9:1) are primarily affected. Extraglandular (systemic) manifestations are seen in one third of patients with Sjogren’s syndrome. Among the extraglandular manifestations, renal involvement is commonly seen. Renal involvement in the form of tubulointerstitial nephritis (TIN) is more common compared to glomerular involvement. Distal renal tubular acidosis (RTA) is more common manifestation of TIN presenting as mild hypokalemia, metabolic acidosis, and rarely with hypokalemic periodic paralysis. We report three cases of hypokalemic periodic paralysis with metabolic acidosis, two in respiratory paralysis, diagnosed as distal RTA. On further evaluation of distal RTA, the patient diagnosed to have Sjogren’s syndrome and managed accordingly. Our report shows that Sjogren’s syndrome is a rare but important cause of hypokaemic periodic paralysis due to RTA.

Don’t pin it all on a stereotype

Hypercalcemia is one of the most frequently encountered problems in endocrinology OPD. Although the evaluation may not always be straightforward in all scenarios. Common factors affecting calcium levels such as dehydration, improper sample collection, and vitamin D supplementation may mask a serious underlying disorder. Here, we discuss a case of an elderly female who had symptoms of myelopathy and hypercalcemia whose etiology was initially attributed to excessive sup

Hipomineralización Incisivo Molar en paciente pediátrico con acidosis tubular renal distal. Reporte de caso. Control y seguimiento por 14 años

Introducción: la hipomineralización incisivo molar es un defecto sistémico del desarrollo que afecta a uno o más primeros molares permanentes, se asocia con frecuencia a los incisivos permanentes, de etiología multifactorial y con diversas opciones de tratamiento. Objetivo: se presenta el caso de un paciente que presenta hipomineralización incisivo molar en sus primeros molares permanentes con antecedentes de haber padecido de acidosis tubular renal distal, dicha entidad puede ocasionar defectos en el esmalte. Reporte del caso: masculino de 7 años de edad diagnosticado con acidosis tubular distal a los 4 meses de edad, al momento de la consulta ya superado. En sus primeros molares permanentes se observan lesiones sugestivas de hipomineralización incisivo molar. Se evalúa clínica y radiográficamente. Se le realizan restauraciones con vidrio ionomérico revisadas en controles semestrales y a los 10 años se decide colocar resinas compuestas en los molares afectados. Se indican controles periódicos a los cuales asiste regularmente por 14 años. Conclusión: la identificación temprana de la Hipomineralización incisivo molar permitirá la aplicación de medidas preventivas para asegurar la permanencia de los dientes afectados en boca. Es Importante afianzar las prácticas higiénicas especialmente en las superficies afectadas, concomitantemente con la aplicación de materiales restauradores.

Introdução: a hipomineralização molar incisivo é um defeito sistémico do desenvolvimento que afeta um ou mais primeiros molares permanentes, está frequentemente associada a incisivos permanentes, de etiologia multifatorial e com várias opções de tratamento. Objetivo: é apresentado o caso de um paciente que apresenta hipomineralização molar incisivo em seus primeiros molares permanentes com histórico de ter sofrido acidose tubular renal distal, esta entidade pode causar defeitos de esmalte. Relato de caso: menino de 7 anos de idade diagnosticado com acidose tubular distal aos 4 meses de idade, à época da consulta já ultrapassado. Em seus primeiros molares permanentes, foram observadas lesões sugestivas de hipomineralização molar incisivo. É avaliado clínica e radiograficamente. Restaurações de ionômero de vidro foram realizadas, revisadas em controles semestrais, e aos 10 anos foi decidido colocar resinas compostas nos molares afetados. São indicados controles periódicos, que frequenta regularmente há 14 anos. Conclusão: a identificação precoce da hipomineralização molar incisivo permitirá a aplicação de medidas preventivas para garantir a permanência dos dentes acometidos na boca. É importante reforçar as práticas de higiene, principalmente nas superfícies afetadas, então com a aplicação de materiais restauradores.

Summary Introduction: molar incisor hypomineralization is a systemic developmental defect that affects one or more permanent first molars, is frequently associated with permanent incisors, of multifactorial etiology and with various treatment options. Objective: the case of a patient who presents molar incisor hypomineralization in his first permanent molars with a history of having suffered from distal renal tubular acidosis is presented, this entity can cause enamel defects Case report: 7-year-old male diagnosed with distal tubular acidosis at 4 months of age, at the time of the consultation he had already passed. In his first permanent molars, lesions suggestive of molar incisor hypomineralization were observed. It is evaluated clinically and radiographically. Glass ionomer restorations were performed, reviewed at six-monthly controls, and at 10 years it was decided to place composite resins on the affected molars. Periodic controls are indicated, which he regularly attends for 14 years. Conclusion: early identification of molar incisor hypomineralization will allow the application of preventive measures to ensure the permanence of affected teeth in the mouth. It is important to strengthen hygienic practices, especially on affected surfaces, concomitantly with the application of restorative materials.

Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

Hypokalemic paralysis due to distal renal tubular acidosistype 1 in patient of mucormycosison amphotericin B: a case report

A 42-year-old male patient who is a known case of DM and mucormycosison treatment presented with sudden onset difficulty in moving all 4 limbs followed by decreased depth of respiration for 4 hours. The patient was known case of DM for 10 years and was on OHA for the same, he had history of biopsy diagnosed rhino mucormycosis 4 months ago and was on treatment for the same. On initial examination the tone was hypotonic in all4 limbs along with power of 3+, respiration was shallow and patient was bedridden unable to stand on his own, he was ambulatory 6 days before presentingto hospital. Potassium-1.7 mEq/l, ABGA pH-7.18, HCO3-10 Meq/l, urine osmolality 220 mOsm/l, urine pH-7.0, potassium-to-creatinine rstio (K/Cr)-3.9 mEq/ml, urine K-22 mEq/ml. Distal RTA (dRTA) is the classical form of RTA, being the first described. DistalRTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalatedcellsof themedullary collecting ductof thedistalnephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to apHof less than 5.3.This case study enumerates the potentially dangerous side effects of amphotericin B in patients which canprecipitate RTA type 1 leading to severe hypokalaemia and acidosis, thus all patients receiving amphotericin B should be cautiously warned regarding side effect of hypokalaemia and prophylactic potassium syrup supplementation may be given in predisposed patients.

Renal tubular acidosis associated with trimethoprim-sulfamethoxazole poisoning / Acidosis tubular renal asociada a intoxicación por trimetoprim-sulfametoxazol

Abstract The combination of trimethoprim-sulfamethoxazole (TMP-SMZ or cotrimoxazole) has a bactericidal effect on gram-positive cocci and gram-negative bacilli. It is used clinically for skin and soft tissue, respiratory and urinary tract infections, and is also relevant for prophylaxis and treatment of opportunistic infections in immunosuppressed patients. Its use at established doses in immunocompetent patients is safe, with a low rate of adverse events. However, in immunosuppressed individuals (human immunodeficiency virus [HIV], transplants, or steroid users), the adverse effects (AEs) of this medication reach 83%; and, when administered parenterally at high doses, lactic acidosis has been documented secondary to the polyethylene glycol vehicle. We present two cases of patients who ingested an overdose of TMP-SMZ and developed type 2 renal tubular acidosis (RTA), which has not been described with this medication, and whose hyperlactatemia is not explained by the polyethylene glycol excipient, as it was taken orally.

Resumen La combinación de trimetoprim-sulfametoxazol (TMP-SMZ o cotrimoxazol) tiene efecto bactericida sobre cocos gram positivos y bacilos gram negativos, con uso clínico en infecciones de piel y tejidos blandos, del tracto respiratorio y urinario, además con relevancia en la profilaxis y tratamiento de infecciones oportunistas en pacientes inmunosupresos. Su uso en pacientes inmunocompetentes a dosis establecidas es seguro, con una baja tasa de eventos adversos. Sin embargo, en población con inmunosupresión: virus de inmunodeficiencia humana (VIH), trasplante, o usuarios de esteroides; los efectos adversos (EA) por este medicamento alcanzan 83% y por administración parenteral en dosis elevadas se ha documentado acidosis láctica secundaria al vehículo polietilenglicol. Presentamos dos casos de pacientes que ingirieron TMP-SMZ en sobredosis, desarrollando acidosis tubular renal (ATR) tipo 2, la cual no se ha descrito en este medicamento y cuya hiperlactatemia no es explicable por el excipiente polietilenglicol debido a que el consumo fue oral.

Oral manifestations of renal tubular acidosis associated with secondary rickets: case report / Manifestações bucais da acidose tubular renal associada ao raquitismo secundário: relato de caso

ABSTRACT This report describes the oral manifestations of renal tubular acidosis (RTA) associated with secondary rickets and discusses the biological plausibility of these findings. The characteristic electrolyte changes during RTA or genetic mutations that trigger RTA may be responsible for impaired amelogenesis, dental malocclusion, impacted teeth, and absent lamina dura. This report reinforces the possibility of an association between RTA and the oral manifestations described.

RESUMO Este relato de caso descreve as manifestações bucais da acidose tubular renal (ATR) associada ao raquitismo secundário e discute a plausibilidade biológica desses achados. As alterações eletrolíticas características da ATR ou as mutações genéticas que a desencadeiam podem ser responsáveis pela amelogênese imperfeita, maloclusão dentária, dentes impactados e ausência de lâmina dura. Este relato reforça a possibilidade de uma associação entre ATR e as manifestações bucais descritas.

Acidosis tubular renal como presentación clínica de Síndrome de Sjögren: reporte de caso / Renal tubular acidosis as a clinical presentation of Sjögren Syndrome: case report

Presentamos el caso clínico de una mujer en la quinta década de la vida, de nacionalidad argentina, que acudió a la guardia de clínica médica de un hospital de tercer nivel por cuadro de mialgias y paresia en las cuatro extremidades, de inicio agudo, progresivo, con dificultad para la movilización de miembros superiores, bipedestación y marcha. Se constató hipocalemia severa, acidosis metabólica, pH urinario alcalino, brecha aniónica urinaria positiva (excreción de amonio), hipocitraturia e hipercalciuria, por lo que se diagnosticó Acidosis Tubular Renal (ATR) tipo I; además se evidenció elevación de creatinkinasa (CK) e insuficiencia renal aguda que corrigió con la reposición de líquidos. Al interrogatorio dirigido, la paciente refirió síndrome seco asociado a artralgias, de varios años de evolución, por lo que se realizaron estudios complementarios que apoyaron el diagnóstico de Síndrome de Sjögren.

We present the clinical case of a woman in the fifth decade of life, argentina, who went to the Internal Medicine emergency room of a third level hospital for symptoms of myalgia and paresis in all four extremities, acute onset, progressive, with difficulty for the mobilization of members superior, standing and walking. Severe hypokalemia, metabolic acidosis, alkaline urinary pH, positive urinary anion GAP (ammonium excretion), hypocitraturia and hypercalciuria were diagnosed. Renal Tubular Acidosis (RTA) type I was diagnosed; acute renal failure was also noted, which corrected with the treatment and elevated creatine kinase (CK). In the anamnesis, the patient reported dry syndrome associated with arthralgias of years of evolution, so that complementary studies were carried out that supported the diagnosis of Sjögren's Syndrome (SS).

Normal anion gap metabolic acidosis secondary to topiramate intake: case report

ABSTRACT Introduction: Topiramate is a drug used to treat various types of epilepsy and as prophylaxis in cases of migrainous headache. One of its mechanisms of action is the inhibition of carbonic anhydrase in the kidney that triggers the excretion of alkaline urine resulting in metabolic acidosis. Case presentation: 17-year-old female patient from Mexico City who regularly uses topiramate, quetiapine and sertraline for the management of depressive disorder. She developed normal anion gap metabolic acidosis secondary to topiramate intake. As a result, she required invasive ventilatory support due to reduced consciousness and respiratory distress. Adequate response to management with laxatives and bicarbonate was achieved, with full renal and neurological recovery. Discussion: Metabolic acidosis is the most common acid-base disorder observed in clinical practice. The difference between measurable cations and anions, known as anion gap, helps to classify the severity of acidosis. Bicarbonate losses or renal tubular disorders generate normal anion gap acidosis as opposed to acidosis resulting from an overproduction of endogenous acid or renal failure, which causes high anion gap. Topiramate is a little known cause of normal anion gap metabolic acidosis; by inhibiting carbonic anhydrase, it causes mixed renal tubular acidosis or type 3 acidosis, as a consequence of the inability to secrete hydrogen ions in the collecting tubule, and a limitation of bicarbonate reabsorption in the proximal tubule. Conclusion: Topiramate, either in therapeutic doses or in overdose, can lead to normal anion gap metabolic acidosis due to the inhibition of carbonic anhydrase in the kidneys. It is usually reversible after starting bicarbonate.

RESUMEN Introducción. El topiramato es un medicamento que se usa en el tratamiento de varios tipos de epilepsia y como profilaxis en casos de cefalea migrañosa. Entre sus mecanismos de acción, la inhibición de la anhidrasa carbónica en el riñón desencadena la excreción de orina alcalina ocasionando acidosis metabólica. Presentación del caso. Paciente femenino de 17 años procedente de la Ciudad de México con antecedente de consumo de topiramato, quetiapina y sertralina para manejo de síndrome depresivo, quien desarrolla acidosis metabólica de anión restante normal secundaria a ingesta de topiramato. La joven requiere soporte ventilatorio invasivo por deterioro del estado de conciencia y síndrome de dificultad respiratoria y presenta adecuada respuesta a manejo con catártico y bicarbonato sin compromiso renal y sin secuelas neurológicas. Discusión. La acidosis metabólica es la alteración ácido base más frecuente en la práctica clínica. La diferencia entre cationes y aniones medibles, conocida como anión restante o brecha aniónica, permite clasificar este tipo de acidosis. Las pérdidas de bicarbonato o trastornos de la función tubular renal generan acidosis de anión restante normal; por el contrario, la acidosis causada por sobreproducción de ácido endógeno o por insuficiencia renal genera anión restante elevado. El topiramato es una causa poco conocida de acidosis metabólica con anión restante normal; al inhibir la anhidrasa carbónica, se ocasiona una acidosis tubular renal mixta o tipo 3 debido a una in capacidad de secreción de hidrogeniones en el túbulo colector y una limitación en la reabsorción del bicarbonato en el túbulo proximal. Conclusión. El topiramato en dosis terapéutica o en sobredosis puede generar acidosis metabólica de anión restante normal debido a la inhibición de la anhidrasa carbónica a nivel renal. Se trata de un cuadro reversible en el cual el manejo con bicarbonato ha mostrado buenos resultados clínicos.

Bilateral Proximal Femur Fractures in a Patient with Renal Tubular Acidosis: A Case Report

@#The diagnosis of pathological fractures is on the rise. Themorbidity involved does not only burden the patient and theirfamilies but it has a great toll on the healthcare system aswell. Early identification of the patient at risk is aninvaluable tool to cut cost and improve the patient’s qualityof life. Multiple renal pathologies have been highlighted inrelation to the risk of pathological fractures; however,complications in renal tubular acidosis have been rarelydocumented. Nevertheless, prompt action with adequate andrelevant patient education ultimately can reduce theassociated morbidity. We present a case of poor control ofthe disease and its debilitating pathological fracturecomplications.

Adult Idiopathic Renal Fanconi Syndrome: A Case Report

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

Etiology and pathogenesis of hereditary renal tubular acidosis / 中华实用儿科临床杂志

Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap due to reduced urinary acidification.Multiple mechanisms act in the renal tubule to maintain balance in hydrogen ion secretions and bicarbonate absorption.In recent years,more and more proteins have been found to be associated with RTA,so hereditary RTA has attracted people's attention.Mutations in the gene SLC4A1,encoding C1-/HCO3-exchanger (kAE1);in the gene ATP6V1B1,encoding B1 subunit of H+-ATP ase;in the gene ATP6V0A4,encoding a4 subunit of H +-ATP ase;in the gene SLC4A4,encoding Na+/HCO3-cotransporter(kNBCe1);in the gene CA2,encoding carbonic anhydrase Ⅱ are identified in the pathogenesis of hereditary RTA.The search for pathogenetic genes for clinically suspected hereditary RTA patients can help us to make accurate genetic diagnosis and provide targeted treatment interventions.

The distal renal tubular acidosis caused by ATP6V1B1 gene mutation:a case report / 临床儿科杂志

Objective To explore the clinical features and gene diagnosis of the distal renal tubular acidosis (dRTA). Methods The clinical data and gene detection results of one child with dRTA were retrospectively analyzed. The related literatures were reviewed. Results Four-month-old female was admitted with frequent vomiting and hearing impairment. The laboratory examination showed refractory hypokalemia and it was difficult to correct metabolic acidosis. Gene detection found a new mutation on ATP6V1B1 gene. The diagnosis of dRTA was confirmed. Conclusions dRTA is a rare disease, ATP6V1B1 gene is the causative gene of the dRTA with sensorineural deafness.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

A case of primary sjogren`s syndrome with distal renal tubular acidosis presenting as hypokalemic paralysis.

Renal tubular acidosis secondary to autoimmune interstitial nephritis is quite common in patients with Sjogren`s syndrome. Here we present a case of 24 year old female who presented with Acute Hypokalemic Quadriparesis and was later diagnosed with distal RTA. Patient did not have features of xerostomia or xerophthalmia but was diagnosed to have Primary Sjogren`s syndrome fromserological findings,in this case renal involvement preceded subjective Sicca syndrome.Patient recovered after giving i.v potassium. Patient was treated with corticosteroids and is asymptomatic during the one year follow up period.

Primary Sjogrens Syndrome with Renal Tubular Acidosis with Central Pontine Myelinolysis – A rare case report

A middle aged female patient, a case of Primary Sjogren’s Syndrome with renal tubular acidosis as revealed by severe hypokalemia along with normal anion gap, metabolic acidosis and acidic urinary pH had brain stem lesion which presented as quadriplegia, dysphagia and dysarthria. Laboratory tests revealed that anti-nuclear antibodies (ANA) and anti Ro/SSA antibodies were positive. MRI showed hyper intense lesion in T2W images in middle pons, typical characteristic of central pontine myelenolysis. So, patient was diagnosed as Primary Sjogren’s Syndrome with renal tubular acidosis with central pontine myelinolysis. She recovered with correction of hypokalemia, intravenous methyl prednisolone and cyclophosphamide.

Approach to the patient with hypokalemia caused by Hashimoto′s thyroiditis associated with primary Sjogren′s syndrome and renal tubular acidosis / 中华内分泌代谢杂志

Hypokalemia is a common clinical symptom. It is quite important to clarify the cause of hypokalemia. Autoimmune thyroid disease and primary Sjogren syndrome ( pSS ) have a common genetic predisposition. The coexistence of both diseases is frequent. Renal tubular acidosis ( RTA) is one of the causes of hypokalemia, which can be primary and secondary to other diseases in etiology. Primary RTA is more common in children. As for adults, RTA is often secondary to pSS. In this paper, we reported a case of hypokalemia caused by Hashimoto’s thyroiditis associated with primary Sjogren’s syndrome and renal tubular acidosis in order to call attention to the special cause and treatment of hypokalemia.

Sequenciamento total do exoma como ferramenta de diagnóstico de acidose tubular renal distal / Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis

Resumo Objetivo A acidose tubular renal distal (ATRd) é caracterizada por acidose metabólica devido à excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd com uso do sequenciamento total do exoma. Métodos Selecionamos duas famílias não relacionadas, quatro crianças com ATRd e seus pais, para fazer o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve perda auditiva severa. Fizemos o sequenciamento total do exoma em dois conjuntos de amostras e confirmamos os achados com o método de sequenciamento de Sanger. Resultados Duas mutações foram identificadas nos genes ATP6V0A4 e ATP6V1B1. Na família um, detectamos uma nova mutação no éxon 13 do gene ATP6V0A4 com uma alteração em um nucleotídeo único GAC → TAC (c.1232G>T) que causou substituição de ácido aspártico por tirosina na posição 411. Na família dois, detectamos uma mutação recorrente do homozigoto com inserção de um par de bases (c.1149_1155insC) no éxon 12 do gene ATP6V1B1. Conclusão Nossos resultados confirmam o valor do sequenciamento total do exoma para o estudo de nefropatias genéticas complexas e permitem a identificação de mutações novas e recorrentes. Adicionalmente, demonstramos claramente pela primeira vez a aplicação desse método molecular em doenças tubulares renais.

Abstract Objective Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis due to impaired renal acid excretion. The aim of this study was to demonstrate the genetic diagnosis of four children with dRTA through use of whole-exome sequencing. Methods Two unrelated families were selected; a total of four children with dRTA and their parents, in order to perform whole-exome sequencing. Hearing was preserved in both children from the first family, but not in the second, wherein a twin pair had severe deafness. Whole-exome sequencing was performed in two pooled samples and findings were confirmed with Sanger sequencing method. Results Two mutations were identified in the ATP6V0A4 and ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the ATP6V0A4 gene with a single nucleotide change GAC → TAC (c.1232G>T) was found, which caused a substitution of aspartic acid to tyrosine in position 411. In the second family, a homozygous recurrent mutation with one base-pair insertion (c.1149_1155insC) in exon 12 of the ATP6V1B1 gene was detected. Conclusion These results confirm the value of whole-exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated.

HIV Infection Itself may be a Cause of Hypokalemic Distal Renal Tubular Acidosis without Hypergammaglobulinemia.

Distal renal tubular acidosis (dRTA) is seen in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) population in the setting of hypergammaglobulinemia and antiretroviral agents, whereas isolated HIV infection is rarely reported to be associated with dRTA. We report a case of a young woman with a history of untreated HIV/AIDS who presented with profound generalized weakness and refractory hypokalemia along with non-anion gap metabolic acidosis and inappropriately high urine pH. Her serum gamma-globulin level was not significantly elevated and she was not on highly active antiretroviral therapy (HAART). No other cause of dRTA was evident. Subsequently, a diagnosis of dRTA secondary to isolated HIV/AIDS was made. Distal RTA can be acquired or inherited and is caused by defects in proton pumps or pH pressure gradients. In dRTA, the potassium level can be low, normal, or even high depending upon the pathophysiologic abnormality. Early recognition and prompt treatment is imperative to avoid the serious consequences of severe electrolyte and metabolic disturbances. Our case report is a reminder to clinicians to be mindful of this rare condition when evaluating unexplained dRTA and to include HIV/AIDS as part of the differential diagnosis of dRTA even in the absence of significant hypergammaglobulinemic (IgG level was slightly elevated) state or antiretroviral agents. We believe this is the second such case to be documented.