ESPE Abstracts (2018) 89 P-P3-237

Growth Hormon Deficiency in Identical Twins with Gitelman Syndrome due to Compound Heterozygous Mutation (p.R80fs*35/p.K957X) of the SLC12A3 Gene and the Evaluation of the Response to Growth Hormone Replacement Therapy

Betul Yamana, Kubra Celegenb, Emine Korkmazb, Naz Guleray Lafcic, Zeynep Balikd, Huseyin Demirbileka & Ali Duzovab


aHacettepe University Faculty of Medicine, Department of Paediatric Endocrinology, Ankara, Turkey; bHacettepe University Faculty of Medicine, Department of Paediatric Nephrology, Ankara, Turkey; cHacettepe University Faculty of Medicine, Department of Genetics, Ankara, Turkey; dHacettepe University Faculty of Medicine, Department of Paediatrics, Ankara, Turkey


Background: Gitelmann syndrome, a rare autosomal recessive disorder, is characterised with hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Mutations in the SLC12A3 gene, which encodes for ‘Thiazid sensitive sodium chloride co-transporter channels’ located at the renal distal convoluted tubules account for the underlying molecular mechanism of Gitelmann syndrome. Although, is less frequent than those seen in ‘Bartter Syndrome’, the exact mechanism of growth retardation in Gitelmann syndrome has not been elucidated.

Case reports: Male identical twins presented at the age of 14.4 years-old with complaints of short stature which was recognised about the age of 8–10 years. Both patients was on magnesium and potassium replacement therapy for hypomagnesemia and hypokalemia. The antropometric measurements, bone age and pubertal findings at presentation are shown in Table 1. Serum IGF1 and IGFBP3 levels were low, both cases had low growth rates and inadequate peak growth hormon (GH) response to the GH stimulation tests (Table 1). A diagnosis of Gitelmann Syndrome and GH deficiency was considered and GH replacement therapy was added to the therapy. Pituitary MRI and other pitutary hormones were normal for both cases. Assessment of the GH therapy at 9th month revealed an increase in IGF1 levels and growth rates, with accompanying progression of puberty; though the response to GH therapy was not satisfactory, particularly in case 1. Unsatisfactory response to GH replacement therapy was attributed to the poor compliance to the therapy and frequent hospital admissions due to recurrent episodes of electrolyte imbalance. In the mutation analysis a compound heterozygous mutation (p.R80fs*35/p.K957X) was detected in the SLC12A3 gene, which confirmed the diagnosis of Gitelmann syndrome.

Table 1
Case 1Case 2
Weight (kg)32.735.5
Height (cm)145.5 (−2.88 S.D.)149.2 (−2.39S.D.)
Testicular volume (ml)4/44/6
Bone age (year)1013
IGF1 (ng/ml)80.7 (−2.41S.D.)110.7 (−2.06S.D.)
IGFBP3 (ng/ml)2219 (−2.31S.D.)2124 (−2.37S.D.)
Growth rate (cm/year)1.63.2
L-dopa test peak GH (ng/ml)4.60.09
Clonidine test peak GH (ng/ml)4.32 0.716
GH dose (mg/kg/day)0.0330.033
Growth rate with GH therapy (cm/year)5.37.7
IGF1 (Under GH therapy)(ng/ml)293.4296.0
Mutationp.R80fs*35/p.K957Xp.R80fs*35/p.K957X

Conclusion: Gitelmann syndrome patients with short stature should be investigated for GH-IGF-1 axis disturbances. For optimal growth, in addition to correcting serum potassium, GH replacement may be considered. However, in order to further assess the response to GH replacement therapy, more experiences are required.