Endocrine Abstracts

Gitelman’s syndrome (GS) is an autosomal recessive renal tubular disorder caused by mutations of the SLC12A3 gene coding for the thiazide-sensitive sodium chloride co-transporter (NCCT). Hypokalaemia, hypomagnesaemia, hypocalciuria and metabolic alkalosis are consequent. Sjorgren’s syndrome (SS) is a connective tissue disorder primarily affecting lacrimal and salivary glands resulting in sicca complex. The coincidental presence of both syndromes is rare. A 28 year old female presented with hypokalaemia (2.8 mmol/l) and hypomagnesaemia (0.52 mmol/l). Potassium levels 3 and 17 years earlier were 3.5 and 3.4 mmol/l respectively. Six months earlier a diagnosis of SS was made when she presented with a painful, swollen right parotid gland. Anti-ENA, ANA, anti-Ro and rheumatoid factor were all positive. At 7 and 12 years of age painful, swollen left and right submandibular glands respectively were removed without diagnosis. Review of the histology however suggested a diagnosis of paediatric Sjorgren’s syndrome. Investigations confirmed normal renal function, venous pH 7.46, bicarbonate 28 mmol/l, hypocalciuria (0.97 mmol/24 hours), PRA 13.9 nmol/l/hr and aldosterone 300 pmol/l. SLC12A3 gene analysis confirmed compound heterozygosity with:

1. The known mutation c.460A>T, p.(Ile54Phe) maternal heterozygous carrier, non-affected. 2. A novel c.1258-1262 del, p.ALA (420GLNFS*103) paternal heterozygous carrier, non-affected. There are 10 previous reports of GS coincidental with SS. Two reported heterozygous mutations, 4 reported absence of mutations and in 4 mutations were not sought. The acquired cases of GS were attributed to antibodies to the NCCT.

The apparent late onset of the GS in our case could be due to:

1. Latent hypofunction of NCCTs induced by the compound heterozygous mutations with compensation mechanisms.

2. The development of auto-antibodies to the NCCTs overriding the compensatory mechanisms.

3. A combination of a. and b.