Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short
stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta.
In this study, the authors describe the clinical manifestations, and investigate the
molecular etiology, in a patient with RTA.
The authors report on a girl with distal RTA who carried a novel homozygous base substitution
of 2 consecutive base pair variants (NM_001098484.3:c.808-2A>C and NM_001098484.3:c.808-1G>C)
in the SLC4A4 gene. The patient had clinical manifestations of autoimmune thyroiditis and distal
RTA, including hypercalciuria, nephrocalcinosis, and nephrolithiasis. In addition
to the presence of hypoplastic-type amelogenesis imperfecta, generalized enamel hypomaturation,
a feature seen in mice lacking Slc4a4, was also observed in the patient. The basic defect in this patient appeared to be
impaired hydrogen ion secretion, leading to an inability to acidify the urine, resulting
in alkaline urine (despite a normal serum anion gap), hypokalemic, and hyperchloremic
metabolic acidosis. The pulp stones found in the patient may likely be the consequences
of a disrupted acid-base homeostatic environment that precipitated mineral deposits.
Even with proper treatments for distal RTA, the patient has had frequent recurrences
of band keratopathy, pupillary membrane, and cataract.
This is the first report of distal RTA, autoimmune thyroiditis, tooth agenesis, enamel
hypomaturation, and pulp stones associated with an SLC4A4 mutation. It is important for dentists to be aware that amelogenesis imperfecta in
patients may be a sign of systemic diseases including RTA, nephrocalcinosis, or nephrolithiasis.