Alternative titles; symbols
ORPHA: 47159, 93607;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4q13.3 | Renal tubular acidosis, proximal, with ocular abnormalities | 604278 | Autosomal recessive | 3 | SLC4A4 | 603345 |
A number sign (#) is used with this entry because of evidence that autosomal recessive proximal renal tubular acidosis with ocular abnormalities and impaired intellectual development is caused by homozygous mutation in the SLC4A4 gene (603345) on chromosome 4q13.
Winsnes et al. (1979) reported the cases of 2 brothers with severe hyperchloremic acidosis, a maximum tubular capacity for bicarbonate reabsorption about half normal, growth retardation, mental retardation, nystagmus, cataract, corneal opacities, glaucoma, and defects in the enamel of the permanent teeth. Red cells showed increased osmotic resistance. The possibility of a generalized membrane defect was raised. Also, similarities to Lowe syndrome (309000) were pointed out.
Braverman and Snyder (1987) identified a 5-year-old male who presented with band keratopathy as the first sign of proximal renal tubular acidosis.
Igarashi et al. (1994) described a female who had presented at the age of 16 years with persistent proximal renal tubular acidosis, mental retardation, band keratopathy, cataracts, glaucoma, and short stature. She had an abnormally low renal threshold for bicarbonate reabsorption.
The transmission pattern of proximal renal tubular acidosis with ocular abnormalities and impaired intellectual development in the patients reported by Igarashi et al. (1999) was consistent with autosomal recessive inheritance.
Igarashi et al. (1999) identified a homozygous arg298-to-ser mutation in the SLC4A4 gene (R298S; 603345.0001) in the patient originally described by Igarashi et al. (1994). In a second female, who presented at age 2 years with short stature, acidosis with very low bicarbonate, proximal renal tubular acidosis, mental retardation, and bilateral glaucoma, cataracts, and band keratopathy, they identified homozygosity for an arg510-to-his mutation in the SLC4A4 gene (R510H; 603345.0002).
In a patient with proximal renal tubular acidosis, mental retardation, and bilateral glaucoma, but no cataracts or keratopathy, Igarashi et al. (2001) identified a homozygous gln29-to-ter mutation in the SLC4A4 gene (Q29X; 603345.0003).
Braverman, D. E., Snyder, W. E. A case report and review of band keratopathy. Metab. Pediat. Syst. Ophthal. 10: 39-41, 1987. [PubMed: 3151218]
Igarashi, T., Inatomi, J., Sekine, T., Cha, S. H., Kanai, Y., Kunimi, M., Tsukamoto, K., Satoh, H., Shimadzu, M., Tozawa, F., Mori, T., Shiobara, M., Seki, G., Endou, H. Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. (Letter) Nature Genet. 23: 264-265, 1999. [PubMed: 10545938] [Full Text: https://doi.org/10.1038/15440]
Igarashi, T., Inatomi, J., Sekine, T., Seki, G., Shimadzu, M., Tozawa, F., Takeshima, Y., Takumi, T., Takahashi, T., Yoshikawa, N., Nakamura, H., Endou, H. Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma. J. Am. Soc. Nephrol. 12: 713-718, 2001. [PubMed: 11274232] [Full Text: https://doi.org/10.1681/ASN.V124713]
Igarashi, T., Ishii, T., Watanabe, K., Hayakawa, H., Horio, K., Sone, Y., Ohga, K. Persistent isolated proximal renal tubular acidosis--a systemic disease with a distinct clinical entity. Pediat. Nephrol. 8: 70-71, 1994. [PubMed: 8142230] [Full Text: https://doi.org/10.1007/BF00868266]
Nash, M. A., Torrado, A. D., Griefer, I., Spitzer, A., Edelmann, C. M., Jr. Renal tubular acidosis in infants and children. J. Pediat. 80: 738-748, 1972. [PubMed: 5018384] [Full Text: https://doi.org/10.1016/s0022-3476(72)80124-0]
Rodriguez Soriano, J. R., Boichis, H., Stark, H., Edelmann, C. M., Jr. Proximal renal tubular acidosis: a defect in bicarbonate reabsorption with normal urinary acidification. Pediat. Res. 1: 81-98, 1967. [PubMed: 6029811] [Full Text: https://doi.org/10.1203/00006450-196703000-00001]
Sebastian, A., McSherry, E., Morris, R. C., Jr. On the mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (type 2 RTA). J. Clin. Invest. 50: 231-243, 1971. [PubMed: 5101297] [Full Text: https://doi.org/10.1172/JCI106479]
Winsnes, A., Monn, E., Stokke, O., Feyling, T. Congenital persistent proximal type renal tubular acidosis in two brothers. Acta Paediat. Scand. 68: 861-868, 1979. [PubMed: 44068] [Full Text: https://doi.org/10.1111/j.1651-2227.1979.tb08224.x]