Renal Tubular Acidosis, Proximal, With Ocular Abnormalities And Mental Retardation

A number sign (#) is used with this entry because of evidence that autosomal recessive proximal renal tubular acidosis with ocular abnormalities and mental retardation is caused by homozygous mutation in the SLC4A4 gene (603345) on chromosome 4q13.

Clinical Features

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.

Molecular Genetics

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).