RESUMO
BACKGROUND Gitelman syndrome (GS) is a rare inherited autosomal recessive salt-losing renal tubulopathy. Early-onset GS is difficult to differentiate from Bartter syndrome (BS). It has been reported in some cases that cyclooxygenase (COX) inhibitors, which pharmacologically reduce prostaglandin E2(PGE2) synthesis, are helpful for GS patients, especially in children, but the long-term therapeutic effect has not yet been revealed. CASE REPORT A 4-year-old boy was first brought to our hospital for the chief concern of short stature and growth retardation. Biochemical tests demonstrated severe hypokalemia, hyponatremia, and hypochloremic metabolic alkalosis. The patient's serum magnesium was normal. He was diagnosed with BS and treated with potassium supplementation and indomethacin and achieved stable serum potassium levels and slow catch-up growth. At 11.8 years of age, the patient showed hypomagnesemia and a genetic test confirmed that he had GS with compound heterozygous mutations in the SLC12A3 gene. At the age of 14.8 years, when indomethacin had been taken for nearly 10 years, the boy reported having chronic stomachache, while his renal function remained normal. After proton pump inhibitor and acid inhibitor therapy, the patient's symptoms were ameliorated, and he continued to take a low dose of indomethacin (37.5 mg/d divided tid) with good tolerance. CONCLUSIONS Early-onset GS in childhood can be initially misdiagnosed as BS, and gene detection can confirm the final diagnosis. COX inhibitors, such as indomethacin, might be tolerated by pediatric patients, and long-term therapy can improve the hypokalemia and growth retardation without significant adverse effects.
Assuntos
Síndrome de Bartter , Síndrome de Gitelman , Hipopotassemia , Adolescente , Criança , Pré-Escolar , Humanos , Masculino , Síndrome de Bartter/genética , China , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Transtornos do Crescimento/complicações , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Indometacina/uso terapêutico , Potássio , Membro 3 da Família 12 de Carreador de Soluto/genética , Membro 3 da Família 12 de Carreador de Soluto/metabolismoRESUMO
RATIONALE: The diagnosis of Gentleman syndrome (GS) is usually delayed because the clinical symptoms are easily mistaken. PATIENT CONCERNS: A 19-year-old male patient was referred to endocrinology due to intermittent twitch of extremities for approximately 7 years. DIAGNOSES: The diagnosis of GS was made based on the laboratory and gene detection results. We identified 2 new variants in the SLC12A3 gene [c.857 Aâ >â C (exon7) and c.2089_2095del (exon17)] in his Asian family. INTERVENTIONS: The patient received the treatment of potassium chloride sustained release tablets, potassium magnesium aspartate and spironolactone. After given potassium supplement through enema, his serum potassium level was corrected to normal. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia were improved with a remission of the clinical manifestations. But the patient's condition still could not remain stable for his irregular oral potassium supplementation during the follow-up of nearly 3 months. LESSONS: Our finding broadens the variant spectrum of SLC12A3 and contributes to a more quickly genetic counseling. As a result, when a patient presents with persistent, unspecified, and inadequately treated hypokalemia, tests for GS should indeed be considered. For suspected cases of GS, genetic testing should always be considered in the diagnosis.
Assuntos
Síndrome de Gitelman , Hipopotassemia , Masculino , Humanos , Adulto Jovem , Adulto , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Linhagem , População do Leste Asiático , Mutação , Membro 3 da Família 12 de Carreador de Soluto/genéticaRESUMO
Gitelman syndrome (GS) is a rare renal disorder, and little is known about its impact on pregnancy. We report the successful outcome of pregnancy in a patient with GS that was managed with aggressive oral and intravenous potassium supplementation.
Assuntos
Síndrome de Gitelman , Hipopotassemia , Nefropatias , Gravidez , Feminino , Humanos , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Potássio/uso terapêuticoRESUMO
A 32-year-old woman presented with an incidental finding of hypokalaemia on routine bloods at 9 weeks of a second pregnancy, on a background of lifelong salt craving. Her previous pregnancy was uncomplicated. She had no previous significant medical or family history. Venous blood gases showed a hypokalaemic, normochloraemic metabolic alkalosis. Urinary potassium was elevated. Escalating doses of oral supplementation of potassium, magnesium, sodium and potassium-sparing diuretics were required through the course of pregnancy, in response to regular electrolyte monitoring. These were later weaned and completely stopped post partum. Delivery was uneventful with no maternal or neonatal complications. Genetic testing performed post partum showed heterogenous mutation of SCL12A3 gene.
Assuntos
Síndrome de Bartter , Síndrome de Gitelman , Hipopotassemia , Adulto , Feminino , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Recém-Nascido , Pacientes Ambulatoriais , Gravidez , Primeiro Trimestre da GravidezRESUMO
BACKGROUND: Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome. CASE PRESENTATION: A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery. CONCLUSIONS: Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome.
Assuntos
Síndrome de Gitelman/etiologia , Hipopotassemia/etiologia , Paralisia/etiologia , Síndrome de Sjogren/complicações , Diagnóstico Diferencial , Suplementos Nutricionais , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/tratamento farmacológico , Paralisia/diagnóstico , Paralisia/tratamento farmacológico , Potássio/uso terapêutico , Espironolactona/uso terapêutico , Adulto JovemRESUMO
Gitelman syndrome (GS) is a rare autosomal-recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The impact of GS to pregnant and fetus is not wellknown, with few reports until now and no report about twin pregnancy and GS. We report the successful outcome of monochorionic twin pregnancy in a patient with GS. Oral or intravenously potassium chloride and magnesium citrate were prescribed. The course of the pregnancy was uneventful and the patient remained asymptomatic despite persistent hypokalemia. At 36+4 weeks of gestation, two female babies were delivered, weighing 2,380 and 2,210 g respectively. SLC12A3 gene analysis in mother and two babies revealed heterozygous mutations at 988 ATA codon in exon 26, which convert isoleucine to threonine (I988T). The mother and the twins are all in good health condition during three years follow-up. Close fetal serial surveillance, frequent electrolyte evaluation and adequately supplement with potassium and magnesium should be required to prevent obstetrical and fetal complications in a patient with GS. Management by multidisciplinary team is critical to optimizing outcomes for mother and fetus.
Assuntos
Síndrome de Gitelman , Hipopotassemia , Suplementos Nutricionais , Feminino , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Humanos , Lactente , Mutação , Gravidez , Gravidez de Gêmeos , Membro 3 da Família 12 de Carreador de Soluto/genéticaRESUMO
Chronic hypokalemia is the main finding in patients with Gitelman's syndrome (GS). GS, a variant of Bartter's syndrome, is an autosomal recessive renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. GS is caused by inactivating mutations in the thiazide-sensitive sodium-chloride cotransporter gene. It is also called the "milder" form of Bartter's syndrome, as patients with GS are usually diagnosed in adulthood during routine investigation. Our objective is to highlight the impact of correct distinction between the causes of hypokalemia on management and the need of long-term follow- up after the restoration of normokalemic status. Herein, we report an asymptomatic 40-year-old male, whose persistent hypokalemia was due to GS. The diagnosis was first established by laboratory tests, and he was treated with low-dose aldosterone antagonists (spironolactone), angiotensin-converting enzyme inhibitors, and potassium and magnesium supplements. Genetic testing confirmed the diagnosis of GS and revealed a rare mutation. We conclude that GS is a rare and real diagnostic and therapeutic challenge, for which a close collaboration between endocrinologists and nephrologists is mandatory, as also the thorough genetic investigation of the mutations associated with this syndrome.
Assuntos
Síndrome de Gitelman/genética , Hipopotassemia , Mutação/genética , Adulto , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/etiologia , Masculino , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Membro 3 da Família 12 de Carreador de Soluto/genética , Espironolactona/uso terapêuticoRESUMO
An 8-year-old girl with recently diagnosed Systemic Lupus Erythematosus (SLE) (class 4 lupus nephritis with autoimmune hemolytic anemia) presented to the pediatric nephrology clinic with polyuria, tiredness and cramps; laboratory investigations revealed refractory hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria and hyperchloriuria. There was no history of diuretic administration. These features were consistent with the Gitelman syndrome. She required large doses of potassium and magnesium supplementation along with spironolactone, for normalization of the serum potassium and magnesium levels. Immunosuppressive therapy was continued with cyclophosphamide pulses administered on a monthly basis. The doses of potassium and magnesium supplements were tapered off over the next 6 months. The clinical exome sequencing was negative for any mutations in the SLC12A3 gene. An 'acquired' form of Gitelman syndrome has been reported earlier in association with Sjogren syndrome and systemic sclerosis. Though tubular disorders such as renal tubular acidosis have been reported in association with SLE, a Gitelman-like syndrome has not been reported earlier. This case adds Gitelman-like tubulopathy to the clinical spectrum of tubular disorders complicating SLE.
Assuntos
Síndrome de Gitelman/etiologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/complicações , Poliúria/diagnóstico , Alcalose/diagnóstico , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Feminino , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/urina , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/tratamento farmacológico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Túbulos Renais/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/patologia , Magnésio/administração & dosagem , Magnésio/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Poliúria/etiologia , Potássio/administração & dosagem , Potássio/uso terapêutico , Indução de Remissão , Espironolactona/administração & dosagem , Espironolactona/uso terapêuticoRESUMO
Gitelman syndrome is an inherited tubulopathy characterized by renal salt wasting from the distal convoluted tubule. Defects in the sodium chloride cotransporter (encoded by SLC12A3) underlie this autosomal recessive condition. This article focuses on the specific challenges of diagnosing and treating Gitelman syndrome, with use of an illustrative case report. Symptoms relate to decreased serum potassium and magnesium levels, which include muscle weakness, tetany, fatigue and palpitations. Sudden cardiac deaths have been reported. Making a diagnosis may be difficult given its rarity but is important. A knowledge of the serum and urine biochemical picture is vital to distinguish it from a broad differential diagnosis, and application of genetic testing can resolve difficult cases. There is a group of Gitelman syndrome heterozygous carriers that experience symptoms and electrolyte disturbance and these patients should be managed in a similar way, though here genetic investigations become key in securing a difficult diagnosis. Potassium and magnesium replacement is the cornerstone of treatment, though practically this can be hard for patients to manage and often does not fully relieve symptoms even when serum levels are normalized. Challenges arise due to the lack of randomized controlled trials focussing on treatment of this rare disease; hence, clinicians endorse strategies in line with correction of the underlying pathophysiology such as sodium loading or pharmacological treatments, which seem to help some patients. Focussed dietary advice and knowing the best tolerated preparations of potassium and magnesium medications are useful tools for the physician, as well as an awareness of the specific burdens that this patient group face in order to signpost appropriate support.
Assuntos
Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/metabolismo , Magnésio/administração & dosagem , Potássio/administração & dosagem , Sódio/administração & dosagem , Idoso , Humanos , MasculinoRESUMO
RATIONALE: The Gitelman's syndrome (GS) is characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. However, the involvement of this deranged electrolyte balance in patients with GS in parathyroid hormone action has not been known. PATIENT CONCERNS: We report a 34-year-old woman with muscle weakness and tetany/seizures caused by electrolyte imbalance. She had hyperphosphatemia and hypocalciuric hypocalcemia in addition to severe hypomagnesemia with low potassium in the absence of metabolic alkalosis. We identified 2 heterozygous mutations in the solute carrier family 12 member 3 gene in this case (c.1732G>A, p.Val578Met and c.2537_38delTT, p.846fs) by targeted sequence for all causative genes of salt-losing tubulopathies. DIAGNOSES: A diagnosis of GS. Hypocalcemia and hyperphosphatemia were suggested to relate with the secondary obstruction of appropriate parathyroid hormone release following severe hypomagnesemia in GS. INTERVENTIONS: She was treated with single oral magnesium oxide administration. OUTCOMES: The electrolyte imbalance including hypocalcemia and hyperphosphatemia were resolved with a remission of clinical manifestations. LESSONS: These observations, in this case, suggest that even severe hypomagnesemia caused by GS was associated with resistance to appropriate parathyroid hormone secretion. Through this case, we recognize that secondary hypoparathyroidism would be triggered by severe hypomagnesemia in GS.
Assuntos
Antiácidos/uso terapêutico , Síndrome de Gitelman/complicações , Síndrome de Gitelman/tratamento farmacológico , Hiperfosfatemia/complicações , Hiperfosfatemia/tratamento farmacológico , Óxido de Magnésio/uso terapêutico , Administração Oral , Adulto , Feminino , Síndrome de Gitelman/genética , Humanos , Hiperfosfatemia/genéticaRESUMO
PURPOSE: Aldosterone proinflammatory/profibrotic effects are mediated by the induction of mononuclear leucocytes (MNL) to express oxidative stress (OxSt)-related proteins, such as p22phox, and by the activation of RhoA/Rho kinase pathway. Gitelman's syndrome (GS), an autosomal recessive tubulopathy, is an interesting opposite model to hypertension, being characterized by hypokalemia, activation of renin-angiotensin-aldosterone system yet normo/hypotension and lack of cardiovascular-renal remodeling. We aimed to evaluate the proinflammatory/profibrotic effect of aldosterone in MNL of 6 GS patients compared with 6 healthy subjects (HS). METHODS: p22phox expression and MYPT-1 phosphorylation status, a marker of RhoA/Rho kinase pathway activation, were evaluated in MNL of GS patients and HS at baseline and after incubation with aldosterone (1 × 10-8 M) alone or with canrenone (1 × 10-6 M). RESULTS: At basal condition, p22phox expression was significantly higher in HS than in GS patients (1.02 ± 0.05 densitometric unit (du) vs 0.40 ± 0.1 du, respectively). Aldosterone significantly increased p22phox expression in HS and this effect was reversed by coincubation with canrenone (1.4 ± 0.05 du and 1.09 ± 0.03 du, respectively). No significant change was reported in GS after incubation of MNL with aldosterone and/or canrenone compared with basaline. Even MYPT-1 phosphorylation was significantly higher in HS compared with GS patients at basal condition (1.16 ± 0.1 du vs 0.69 ± 0.07, respectively). Aldosterone significantly increased MYPT-1 phosphorylation only in HS (1.37 ± 0.1 du vs 0.83 ± 0.12 du in GS). CONCLUSIONS: GS patients seem to be protected by the OxSt status induced by aldosterone and revealed in HS. This human model could provide additional clues to highlight the proinflammatory/cardiovascular remodeling effects of aldosterone.
Assuntos
Aldosterona/farmacologia , Fibrose/prevenção & controle , Síndrome de Gitelman/tratamento farmacológico , Hipertensão/tratamento farmacológico , Inflamação/prevenção & controle , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Fibrose/metabolismo , Seguimentos , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/patologia , Humanos , Hipertensão/metabolismo , Hipertensão/patologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , NADPH Oxidases/metabolismo , Fosforilação , Prognóstico , Transdução de Sinais , Adulto JovemRESUMO
Doctors will often see patients with chronic hypokalaemia, frequently this is secondary to gastrointestinal losses, diuretics or renal disease. However, in this case report we review a rarer cause of chronic hypokalaemia-Gitelman syndrome (GS).GS is an uncommon genetic disorder which causes primary renal tubular hypokalaemic metabolic alkalosis with secondary hypomagnesaemia and hypocalciuria. Although rare, it is important to remember GS when considering differential diagnoses for chronic hypokalaemia. We report the case of a woman who presented to the ophthalmology department with sclerochoroidal calcification. An ophthalmologist was reviewing the medical literature, which prompted them to investigate for GS. A diagnosis was formed at that time based on the blood and urine chemistry results. However, later we were able to offer the patient genetic testing, which confirmed our provisional diagnosis.
Assuntos
Síndrome de Gitelman/diagnóstico , Hipopotassemia/diagnóstico , Síndrome de Barth/diagnóstico , Cálcio/urina , Doença Crônica , Diagnóstico Diferencial , Feminino , Síndrome de Gitelman/tratamento farmacológico , Humanos , Hipopotassemia/sangue , Magnésio/sangue , Pessoa de Meia-IdadeRESUMO
In this paper, we present two women with hypokalaemic rhabdomyolysis in the context of increased diuretic intake and gastroenteritis, respectively. While their clinical manifestations and laboratory results were strikingly similar, two different underlying disorders were subsequently unveiled. The first patient was diagnosed with Conn syndrome, and adrenalectomy led to significant improvement of hypertension and sustained normokalaemia. The diagnosis in the second patient was Gitelman syndrome. Electrolyte supplements improved long-term lassitude and the frequency of muscle cramps declined significantly. These case vignettes illustrate the importance of establishing the underlying cause of hypokalaemia.
Assuntos
Síndrome de Gitelman/diagnóstico , Hiperaldosteronismo/diagnóstico , Adrenalectomia , Diagnóstico Diferencial , Suplementos Nutricionais , Feminino , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico por imagem , Síndrome de Gitelman/tratamento farmacológico , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/cirurgia , Hipertensão/etiologia , Hipopotassemia/etiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Potássio/administração & dosagem , Rabdomiólise/etiologia , Adulto JovemRESUMO
BACKGROUND: Gitelman syndrome (GS), an inherited autosomal recessive salt-losing renal tubulopathy caused by mutations in SLC12A3 gene, has been associated with normal prostaglandin E2 (PGE2) levels since 1995 by a study involving 11 clinically diagnosed patients. However, it is difficult to explain why cyclooxygenase-2 (COX2) inhibitors, which pharmacologically reduce PGE2 synthesis, are helpful to patients with GS, and few studies performed in the last 20 years have measured PGE2 levels. The relationships between the clinical manifestations and PGE2 levels were never thoroughly analyzed. METHODS: This study involved 39 GS patients diagnosed by SLC12A3 gene sequencing. Plasma and 24-h urine samples as well as the clinical data were collected at admission. PGE2 and PGEM levels were detected in plasma and urine samples by enzyme immunoassays. The in vivo function of the sodium-chloride co-transporter (NCC) in GS patients was evaluated using a modified thiazide test. The association among PGE2 levels, clinical manifestations and the function of NCC in GS patients were analyzed. RESULTS: Significantly higher levels of urinary and plasma PGEM were observed in GS patients than in the healthy volunteers. Higher urinary PGEM levels indicated more severe clinical manifestations and NCC dysfunction estimated by the increase of Cl- clearance. A higher PGEM level was found in male GS patients, who showed earlier onset age and more severe hypokalemia, hypochloremia and metabolic alkalosis than female GS patients. No relationship between renin angiotensin aldosterone system activation and PGEM level was observed. CONCLUSIONS: Higher urinary PGEM levels indicated more severe clinical manifestations and NCC dysfunction in GS patients. COX2 inhibition might be a potential therapeutic target in GS patients with elevated PGEM levels.
Assuntos
Dinoprostona/sangue , Dinoprostona/urina , Síndrome de Gitelman/sangue , Síndrome de Gitelman/urina , Adolescente , Adulto , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Dinoprostona/metabolismo , Feminino , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Humanos , Modelos Logísticos , Masculino , Mutação/genética , Membro 3 da Família 12 de Carreador de Soluto/genética , Membro 3 da Família 12 de Carreador de Soluto/metabolismo , Adulto JovemRESUMO
Acquired Gitelman's syndrome (GS) associated with Sjögren syndrome (SS) is rare. A 50-year-old woman was admitted to our department because of nausea, acratia and sicca complex. Laboratory tests after admission showed renal failure, hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria, all of which met the diagnostic criteria for GS. Diagnostic evaluation identified primary SS as the cause of the acquired GS. Light microscopy of the renal tissue from the patient showed severe membranoproliferative glomerunephritis and tubulointerstitial nephritis. Immunohistochemical staining of the renal tissue showed the absence of sodium-chloride co-transporter (NCCT) in distal convoluted tubules. Genetic analysis of chromosomal DNA extracted from the patient's peripheral blood showed SLC12A3 gene heterozygous mutation. The reported case was comprehensively analyzed on the basis of the clinical features, and laboratory, pathological and genetic test findings. The patient has achieved a complete remission after meticulous care and appropriate treatment.
Assuntos
Síndrome de Gitelman/genética , Heterozigoto , Mutação , Síndrome de Sjogren/complicações , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Fenótipo , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Membro 3 da Família 12 de Carreador de Soluto/genética , Resultado do TratamentoRESUMO
Background: Gitelman syndrome (GS) is a rare recessively inherited renal tubulopathy associated with renal potassium (K) and magnesium (Mg) loss. It requires lifelong K and Mg supplementation at high doses that are at best unpalatable and at worst, intolerable. In particular, gastrointestinal side effects often limit full therapeutic usage. Methods: We report here the analysis of a cohort of 28 adult patients with genetically proven GS who attend our specialist tubular disorders clinic, in whom we initiated the use of a modified-release Mg preparation (slow-release Mg lactate) and who were surveyed by questionnaire. Results: Twenty-five patients (89%) preferred the new treatment regimen. Of these 25, 17 (68%) regarded their symptom burden as improved and seven reported no worsening. Of the 25 who were not Mg-treatment naïve, 13 (59%) patients reported fewer side effects, 7 (32%) described them as the same and only 2 (9%) considered side effects to be worse. Five were able to increase their dose without ill-effect. Overall, biochemistry improved in 91% of the 23 patients switched from therapy with other preparations who chose to continue the modified-release Mg preparation. Eleven (48%) improved both their Mg and K mean levels, 3 (13%) improved Mg levels only and in 7 cases (30%), K levels alone rose. Conclusions: Patient-reported and biochemical outcomes using modified-release Mg supplements were very favourable, and patient choice should play a large part in choosing Mg supplements with GS patients.
Assuntos
Suplementos Nutricionais , Síndrome de Gitelman/tratamento farmacológico , Magnésio/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine the gene location of two Gitelman syndrome (GS) family SLC12A3 genes and explore treatments using Chinese medicine (CM) prescriptions. METHODS: In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine (including potassium, Panangin and potassium-sparing diuretics) with CM prescription based on Buyang Huanwu Decoction () and Sijunzi Decoction (). The treatment included three stages, oral potassium chloride for the first 2 weeks (stage 1), potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks (stage 2), CM along with the medicine in stage 2 for the final 2 weeks (stage 3). RESULTS: The three mutations occurring in proband 1 from pedigree I were Thr60Met, 965-1_976del13ins12 (small indels mutation) and Ala122Ala (homozygous silent mutation). Likewise, three mutations, Asn359Lys, Thr382Met and Arg913Gln, appeared in the proband 2 from pedigree II. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L (baseline), 2.5 mmol/L (stage 1), 3.1 mmol/L (stage 2) and 3.9 mmol/L (stage 3) in the proband 1, and 2.8 mmol/L (baseline), 3.1 mmol/L (stage 1), 3.5 mmol/L (stage 2) and 4.3 mmol/L (stage 3) in the proband 2, respectively. The symptoms (numbness of limbs, weakness, palpitations, etc.) of both probands were all alleviated. CONCLUSIONS: The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.
Assuntos
Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Medicina Tradicional Chinesa , Mutação/genética , Adolescente , Sequência de Bases , Análise Mutacional de DNA , Família , Feminino , Humanos , Masculino , Linhagem , Membro 3 da Família 12 de Carreador de Soluto/genéticaRESUMO
Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
Assuntos
Síndrome de Bartter/diagnóstico , Condrocalcinose/etiologia , Suplementos Nutricionais , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome de Bartter/sangue , Síndrome de Bartter/genética , Síndrome de Bartter/urina , Cálcio/urina , Canais de Cloreto/genética , Condrocalcinose/prevenção & controle , Conferências de Consenso como Assunto , Diagnóstico Diferencial , Testes Genéticos , Síndrome de Gitelman/complicações , Síndrome de Gitelman/genética , Humanos , Hipopotassemia/sangue , Hipopotassemia/genética , Magnésio/administração & dosagem , Magnésio/sangue , Magnésio/uso terapêutico , Mutação , Fenótipo , Potássio/administração & dosagem , Potássio/sangue , Potássio/uso terapêutico , Guias de Prática Clínica como Assunto , Qualidade de Vida , Doenças Raras/genética , Cloreto de Sódio na Dieta/uso terapêutico , Membro 3 da Família 12 de Carreador de Soluto/genética , UltrassonografiaRESUMO
Gitelman's syndrome is characterized by hypocalciuria, severe hypomagnesemia, and prominent muscular involvements such as fatigue, weakness, cramps, and tetany. It is due to mutations in the thiazide sensitive NaCl co-transporter in the distal convoluted tubule. The administration of thiazide diuretics may induce a subnormal increase of urinary Cl(-) excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less than normal Cl(-) is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Thus, we report a case of Gitelman's syndrome presenting with quadriparesis diagnosed by using thiazide clearance test.
Assuntos
Síndrome de Gitelman/diagnóstico , Quadriplegia/etiologia , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Predisposição Genética para Doença , Síndrome de Gitelman/complicações , Síndrome de Gitelman/tratamento farmacológico , Síndrome de Gitelman/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Valor Preditivo dos Testes , Membro 3 da Família 12 de Carreador de Soluto/efeitos dos fármacos , Membro 3 da Família 12 de Carreador de Soluto/genética , Membro 3 da Família 12 de Carreador de Soluto/metabolismo , Resultado do TratamentoRESUMO
Gitelman syndrome is an autosomal recessive distal renal tubular disorder caused by defective sodium chloride transporters. Biochemically, it presents with hypokalaemic metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is usually managed with oral potassium supplements and potassium-sparing diuretics. We report a case of a 28-year-old woman whose condition worsened during pregnancy; she became resistant to standard management after delivery of her second child. She was managed in a specialist metabolic clinic through a comprehensive approach including perseverance with oral potassium supplement, weekly intravenous potassium and magnesium infusion, correction of vitamin D level and the offering of appropriate dietary advice; this controlled the patient's symptoms and prevented repeated hospital admissions. In this case report, we illustrate a patient's presentation and diagnosis with Gitelman syndrome, discuss triggers of exacerbation, review the relevant literature in terms of differential diagnoses and provide practical advice on the management of difficult cases in a specialist clinic.