A rare case of congenital distal renal tubular acidosis combined with medullary sponge kidney.

Distal renal tubular acidosis combined with medullary sponge kidney (MSK) is not uncommon in adults, but is rare in infants. We report a 13-month-old boy with MSK who had features of distal renal tubular acidosis (nephrocalcinosis, hypercalciuria, hypocitraturia) and failed to thrive. Renal ultrasound revealed bilateral increased medullary echogenicity and nephrocalcinosis. Bilateral medullary nephrocalcinosis in the ultrasound was the first sign that alerted our pediatrician to the presence of MSK in infants. Earlier treatment may increase efficacy.

[Primary distal renal tubular acidosis]. / Acidose tubulaire rénale distale primitive.

Renal tubular acidosis are forms of metabolic acidosis characterized by an impairment of urinary acidification due to a lack of urine excretion of protons or loss of bicarbonates. Primary distal renal acidosis (dRTA) is characterized by hyperchloremic metabolic acidosis due to failure in proton excretion, variably severe nephrocalcinosis and/or nephrolithiasis associated with hypercalciuria and hypocitraturia. When the metabolic acidosis is compensated, dRTA can be diagnosed by the failure of urinary acidification after oral ammonium chloride or furosemide administration. dRTA is inherited as either an autosomal dominant or autosomal recessive trait. An autosomal dominant form results from a SLC4A1 gene mutation leading to dysfunction of the anionic exchanger type 1 (AE1). Otherwise, recessive forms are due to mutations of ATP6V1B1 gene encoding the B1-subunit of H+-ATPase expressed in the apical membrane of the alpha intercalated cells in collecting duct and in the cochlea. Those mutations lead to dRTA accompanied by sensorineural deafness. Also, mutations in ATP6V0A4 gene encode the accessory subunit a4 of the H+ATPase, leading to recessive forms of dRTA with preserved hearing or delayed signs of deafness. Molecular approach can identify mutations which are responsible for this pathology. The medical treatment is simple and involves an alkali load which allows curing the metabolic acidosis. Long-term outcome is usually good unless the patient's compliance is low or alkalizing treatment is insufficient.

Wide spectrum of clinical features in a case of arthrogryposis-renal tubular dysfunction-cholestasis syndrome.

Arthrogryposis-renal tubular dysfunction-cholestasis syndrome is a rare multisystem disorder, originally described in 1973 and to date only 62 patients have been reported. Herein, we reported on a neonate with arthrogryposis-renal tubular dysfunction-cholestasis syndrome presenting very early after birth. Recurrent febrile illnesses, failure to thrive, ichthyosis, hypothyroidism, and bilateral hearing loss were among other associated findings. Blood films revealed abnormally large platelets. Polyhydramnios, hybrid type of renal tubular acidosis and hypothyroidism found in this case are not usually seen. We propose to expand the acronym of this syndrome and name it as arthrogryposis-renal dysfunction-cholestasis-hypothyroidism-ichthyosis-deafness or dysmorphic features syndrome.

G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis.

Autosomal recessive proximal renal tubular acidosis is caused by mutations in the SLC4A4 gene encoding the electrogenic sodium bicarbonate cotransporter NBCe1-A. The mutations that have been characterized thus far result in premature truncation, mistargeting, or decreased function of the cotransporter. Despite bicarbonate treatment to correct the metabolic acidosis, extrarenal manifestations persist, including glaucoma, cataracts, corneal opacification, and mental retardation. Currently, there are no known therapeutic approaches that can specifically target mutant NBCe1-A proteins. In the present study, we tested the hypothesis that the NBCe1-A-Q29X mutation can be rescued in vitro by treatment with aminoglycoside antibiotics, which are known for their ability to suppress premature stop codons. As a model system, we cloned the NBCe1-A-Q29X mutant into a vector lacking an aminoglycoside resistance gene and transfected the mutant cotransporter in HEK293-H cells. Cells transfected with the NBCe1-A-Q29X mutant failed to express the cotransporter because of the premature stop codon. Treatment of the cells with G418 significantly increased the expression of the full-length cotransporter, as assessed by immunoblot analysis. Furthermore, immunocytochemical studies demonstrated that G418 treatment induced cotransporter expression on the plasma membrane whereas in the absence of G418, NBCe1-A-Q29X was not expressed. In HEK293-H cells transfected with the NBCe1-A-Q29X mutant not treated with G418, NBCe1-A-mediated flux was not detectable. In contrast, in cells transfected with the NBCe1-A-Q29X mutant, G418 treatment induced Na(+)- and HCO(3)(-)-dependent transport that did not differ from wild-type NBCe1-A function. G418 treatment in mock-transfected cells was without effect. In conclusion, G418 induces ribosomal read-through of the NBCe1-A-Q29X mutation in HEK293-H cells. These findings represent the first evidence that in the presence of the NBCe1-A-Q29X mutation that causes proximal renal tubular acidosis, full-length functional NBCe1-A protein can be produced. Our results provide the first demonstration of a mutation in NBCe1-A that has been treated in a targeted and specific manner.

Despistaje de acidosis tubular renal distal en preescolares del jardín de infancia Guiri Guire La Guardia, Estado Nueva Esparta: mayo 2005 / Search of acidosis renal distal in preeschool of the childhood garden Guiri Guire La Guardia, Nueva Esparta: may 2005

La acidosis tubular renal distal es un trastorno congénito o adquirido de la acidificación renal consecuencia de disfunción tubular, no presenta manifestaciones clínicas evidentes. Realizar despistaje en preescolares del Jardín de infancia Guiri Guire, La Guardia, Estado Nueva Esparta, en mayo 2005. Estudio Transversal mixto, muestra de 104 preescolares, se tallaron, pesaron, se llenó cuestionario respecto a hábitos alimentarios. Se realizó examen simple de primera orina en ayunas. Aquellos cuyo pH urinario resultó alcalino y/o presentaban cristales de oxalato de calcio pasaron a segunda etapa del estudio que consistió en recolectar muestra de 1ª y 2ª orina en ayunas, 2 muestras de sangre (en ayunas, post prandial) para determinar electrolitos séricos, urinarios, calcio, creatinina séricos, urinarios, y equilibrio ácido base. Los que presentaron acidosis metabólica hiperclorémica con hiato aniónico urinario positivo, se diagnósticaron como acidosis tubular renal distal. La incidencia es de 1,9 por ciento. Se evidenció alta prevalencia de cristales de oxalato de calcio en orina (26,92 por ciento). Del total se encontró un caso con acidosis metabólica hiperclorémica con hiato aniónico urinario negativo. La asociación entre talla baja y acidosis no fue estadísticamente significativa (p=0,906). La asociación entre déficit ponderal y acidosis no fue significativa (p=0,799). La prevalencia de esta patología (2/104) es significativamente mayor que la mundial (1/10000) (Probabilidad de Poisson = 0,00005352). Se recomienda realizar estudios con muestras de mayor tamaño para resultados más precisos del comportamiento de la enfermedad a nivel estatal.

Siblings with congenital renal tubular acidosis and nerve deafness.

Two siblings (a boy and a girl) had congenital renal tubular acidosis (RTA) with nephrocalcinosis. Hearing loss due to nerve deafness was diagnosed at 13 1/2 and 9 years of age, respectively. The parents, who are second cousins, are healthy. They have another boy who is unaffected. This is in accordance with an autosomal recessive gene. The association of RTA and deafness was first noted by Royer in 1967, and so far some 50 cases have been described. The literature is reviewed.

Primary distal tubular acidosis in childhood: clinical study and long-term follow-up of 28 patients.

The long-term follow-up of 28 patients with congenital primary tubular acidosis is described. Ten patients had affected siblings but no history of similar symptoms in the preceding generation. Deafness was associated in 14 patients and developed before 12 years of age. Deafness was present in all familial cases, and patients without deafness showed no familial incidence, suggesting the existence of two different entities. All patients had growth retardation, which was more severe in the older patients and was always markedly improved by alkaline therapy. Rickets was found in some patients but seemed related to vitamin D deficiency. Catch-up growth was limited to the first 2 years of therapy in patients treated before 2 years of age, but sometimes lasted longer in older patients. Of the 12 patients who reached adulthood, those without rickets achieved a normal height but the others did not. We believe that therapy should be continued throughout life because of the risk of nephrocalcinosis.

Congenital renal tubular dysfunction associated with maternal sniffing of organic solvents.

Two cases of neonatal renal tubular dysfunction and metabolic acidosis due to maternal sniffing of a product containing toluene are reported. Both mothers had been sniffing regularly throughout their pregnancies. The infants were dysmature and had some dysmorphic features. They had hyperchloraemic acidosis and exhibited amino-aciduria. The metabolic changes were however transient. It is suggested that the sniffing of toluene containing solvents during pregnancy may change membrane permeability in both the proximal as well as distal renal tubules and may also enhance liver enzyme activity in the foetus.

[Neonatal ultrasonic detection of medullary nephrocalcinosis associated with Butler-Albright distal tubular acidosis. Apropos of a case]. / Détection échographique néonatale de la néphrocalcinose médullaire associée à l'acidose tubulaire distale de Butler-Albright. A propos d'une observation.

Butler-Albright's distal tubular acidosis was confirmed by ultrasound imaging in the neonatal period, image characteristics showing persistent medullary hyperechogenicity. This case is remarkable by the very early-stage diagnosis of the nephrocalcinosis.

Dental features in congenital persistent renal tubular acidosis of proximal type.

The dental features in a hitherto unknown type of renal tubular acidosis (capillary blood pH 7.07-7.15) of proximal type are reported. The patient presented agenesis of three second premolars, delayed development and eruption of permanent teeth, delayed shedding of the primary dentition and severe enamel hypoplasia of the permanent teeth. Apart from exceptionally thin enamel, histologic, fluorescent and polarization microscopic and microradiographic investigation of three primary teeth did not reveal unusual findings. The changes are most probably due to a generalized, acidosis-induced defect in several highly differentiated ectodermal tissues.

Medullary sponge kidney presenting with hypokalaemic paralysis.

Medullary sponge kidney associated with a defect in urine acidification is rare and usually of no clinical significance. We report a case presenting as hypokalaemic paralysis due to associated congenital distal renal tubular acidosis.

Congenital persistent proximal type renal tubular acidosis in two brothers.

Two brothers showed severe and persistent hyperchloraemic metabolic acidosis (capillary blood pH 7.07--7.15) due to a low renal bicarbonate threshold at 11 mmol/l. The maximal tubular capacity for bicarbonate reabsorption was reduced to about half the normal. A high dose of acetazolamide (25 mg/kg) lowered the tubular bicarbonate reabsorption substantially, indicating the presence of carbonic anhydrase. Both the glomerular filtration rate, the renal blood flow and the renal concentrating capacity were slightly reduced. The clinical characteristics were: growth retardation, mental retardation, nystagmus, corneal opacities, cataract, glaucoma and enamel defects of the permanent teeth. Serum thyroxine was pathological low without clinical signs of hypothyreosis. The erythrocytes showed an increased osmotic resistance. Autopsy of the younger brother, who died 4 1/2 years old, revealed thyroid and thymus weights of 25% of the normal. The kidney tubular cells were swollen with vacuoles. The glomeruli had a normal appearance.