RESUMEN
Glycosuria generally occurs when the threshold for glucose reabsorption by the proximal renal tubule is exceeded or when reabsorption of filtered glucose is impaired. Although the discovery of glycosuria in a child will prompt screening for diabetes mellitus, it is also a sign of a rare tubulopathy called "familial renal glycosuria" (OMIM #233100). This tubulopathy is linked to a defect in the sodium-glucose co-transporter 2, encoded by the SLC5A2 gene. Here, we describe and discuss two pediatric cases in whom familial renal glycosuria was discovered fortuitously after the observation of persistently high urine glucose levels in the absence of hyperglycemia.
Asunto(s)
Glucosuria Renal/diagnóstico , Glucosuria Renal/orina , Adolescente , Biomarcadores/orina , Femenino , Marcadores Genéticos , Pruebas Genéticas , Glucosuria Renal/genética , Humanos , Lactante , Masculino , Mutación , Transportador 2 de Sodio-Glucosa/genéticaRESUMEN
Gordon's syndrome, or type II pseudo-hypoaldosteronism, is a rare cause of arterial hypertension in children. However, it is important to diagnose this syndrome because of the spectacular efficacy of thiazide diuretics. The typical clinical picture of Gordon syndrome includes, apart from arterial hypertension and dyskaliemia, hyperchloremia metabolic acidosis, hypercalciuria, a low rate of renin, and most frequently, a normal or high rate of aldosterone. Dental abnormalities and growth retardation can also be associated. In most cases, it is inherited in an autosomal dominant pattern. We report on a 7-year-old girl who was discovered with arterial hypertension during a consultation for chronic diarrhea. The association of growth retardation, hyperkaliemia, and metabolic acidosis oriented the diagnosis. Starting a thiazide diuretic helped control the arterial hypertension and the kaliemia in a spectacular manner. The genetic analysis proved the existence of a splice mutation on exon 9 of the CUL3 gene coding for cullin 3. This mutation is de novo.
Asunto(s)
Hipertensión/etiología , Seudohipoaldosteronismo/diagnóstico , Niño , Proteínas Cullin/genética , Exones/genética , Femenino , Humanos , Mutación , Seudohipoaldosteronismo/genéticaRESUMEN
Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near-normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non-consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles.
Asunto(s)
Acidosis Tubular Renal/genética , Pérdida Auditiva Sensorineural/genética , Mutación , ATPasas de Translocación de Protón Vacuolares/genética , Adulto , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad/genética , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
BACKGROUND: Hypokalaemic nephropathy has been described in patients with chronic potassium depletion; it is a condition in which proximal tubular vacuolization and interstitial fibrosis occur, resulting in a decline in glomerular filtration rate (GFR) and, in some cases, renal failure. It has been described in patients with chronic diarrhoea, eating disorders, laxative abuse and primary hyperaldosteronism; also occasionally in Bartter syndrome (BS), in which severe hypokalaemia accompanies significant renal sodium and water losses, though rarely in Gitelman syndrome (GS), in which there is equally severe hypokalaemia, but only modest sodium losses. AIM: We hypothesized that hypokalaemic nephropathy may not be due to potassium depletion per se, but persistently elevated circulating levels of aldosterone, possibly with superimposed episodes of renal hypoperfusion. DESIGN AND METHODS: We searched UK and European data sets to retrospectively compare serum and urinary parameters in patients with GS and BS. RESULTS: The patients with GS often had lower serum potassium concentrations than patients with BS, but the BS patients had significantly higher serum creatinine concentrations and lower estimated GFRs (eGFR). BS patients had significantly higher fractional excretions of sodium compared with GS patients, as well as higher plasma renin activities and serum aldosterone levels. CONCLUSION: These findings show that in genetically confirmed cases of BS and GS, the degree of hypokalaemia (as an index of chronic potassium depletion) does not correlate with GFR, and that on-going sodium and water losses, and consequent secondary hyperaldosteronism, may play a more important role in the aetiology of hypokalaemic nephropathy.
Asunto(s)
Síndrome de Bartter/fisiopatología , Síndrome de Gitelman/fisiopatología , Hipopotasemia/fisiopatología , Adulto , Aldosterona/sangre , Síndrome de Bartter/complicaciones , Creatinina/sangre , Femenino , Síndrome de Gitelman/complicaciones , Tasa de Filtración Glomerular , Humanos , Hipopotasemia/complicaciones , Masculino , Potasio/sangre , Renina/sangre , Estudios Retrospectivos , Sodio/orinaRESUMEN
A 23-year-old man presented with osteoporosis, revealed by femoral fractures, and a history of nephrolithiasis, short stature, metabolic acidosis, hypokalemia and ovalocytosis, a red blood cell abnormality common in malaria endemic regions. Biological investigations led to the diagnosis of type 1 distal renal tubular acidosis (dRTA). Ovalocytosis and dRTA may co-exist in the same patient, since both can originate in mutations of the anion-exchanger 1 (AE1) gene, which codes for band 3, the bicarbonate/chloride exchanger, present in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell.
Asunto(s)
Acidosis Tubular Renal , Eliptocitosis Hereditaria/complicaciones , Osteoporosis/complicaciones , Absorciometría de Fotón , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/diagnóstico , Adulto , Proteína 1 de Intercambio de Anión de Eritrocito , Densidad Ósea , Humanos , Masculino , Mutación , Osteoporosis/diagnóstico por imagenRESUMEN
Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performed SSCP analysis of the coding sequence and the exon-intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients with antenatal Bartter syndrome, as well as the identification of three isoforms of human NKCC2 that arise from alternative splicing.
Asunto(s)
Síndrome de Bartter/genética , Proteínas Portadoras/genética , Mutación , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/química , Cloruros , Femenino , Enfermedades Fetales/genética , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Linaje , Potasio , Conformación Proteica , Homología de Secuencia de Aminoácido , Sodio , Simportadores de Cloruro de Sodio-PotasioAsunto(s)
Acuaporinas/genética , Diabetes Insípida Nefrogénica/genética , Mutación Puntual , Receptores de Vasopresinas/genética , Adolescente , Edad de Inicio , Sustitución de Aminoácidos , Acuaporina 2 , Acuaporina 6 , Codón de Terminación , Diabetes Insípida Nefrogénica/orina , Femenino , Mutación del Sistema de Lectura , Humanos , Lactante , Recién Nacido , Masculino , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by renal tubular insensitivity to the antidiuretic effect of arginine vasopressin (AVP). In a large majority of the cases, nephrogenic diabetes insipidus is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, the disease is autosomal recessive or dominant and, for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. Fourteen probands belonging to 12 families were analyzed by single-strand conformational polymorphism and direct sequencing of the AVPR2 and AQP2 genes. Ten mutations of the AVPR2 gene (six previously reported mutations and four novel mutations: G107E, W193X, L43P, and 15delC) were identified. Three mutations of the AQP2 gene were also identified in two patients: the first patient is homozygous for the R85X mutation and the second is a compound heterozygote for V168 M and S216P mutations. Extrarenal responses to infusion of the strong V2 agonist 1-desamino-8-D-arginine vasopressin allowed AVPR2- and AQP2-associated forms of CNDI to be distinguished in three patients. This test also identified an unexpectedly high urinary osmolality (614 mosmol/kg) in a patient with a P322S mutation of AVPR2 gene and a mild form of CNDI.