AME case reports · 2026
A novel variant of SLC12A3 in Gitelman syndrome with hypertension: a case report.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
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Zhang Yu, Guo Zimeng, Gai Ren, Zhou Shanlei, Xia Li, Deng Datong
Аннотация
BACKGROUND: Gitelman syndrome (GS), an autosomal-recessive salt-losing tubulopathy caused by biallelic SLC12A3 variants, classically presents with normo- or hypotension. Hypertension is therefore considered exceptional and may delay diagnosis.
CASE DESCRIPTION: A 19-year-old man was admitted for progressive polyuria, constipation, proximal muscle weakness and fatigue lasting 6 weeks. Laboratory tests showed hypokalaemia (K+ 2.4 mmol/L), hypomagnesaemia (Mg2+ 0.48 mmol/L), hypochloraemia (Cl- 96 mmol/L), hypocalciuria (Ca2+/Cr 0.07 mmol/mmoL) and hyper-reninaemia (plasma renin 52 ng/mL/h; aldosterone 380 pg/mL), together with a paradoxical elevated blood pressure (BP) (152/98 mmHg on three occasions, no medication). Renal ultrasound was normal; 24-h urinary Na+ 210 mmol, K+ 68 mmol, Ca2+ 0.8 mmol. Targeted next-generation sequencing of SLC12A3 disclosed compound-heterozygous variants: (I) c.254C>T (p.Thr85Ile) in exon 1, absent from gnomAD and ClinVar, predicted deleterious by SIFT, PolyPhen-2 and Combined Annotation Dependent Depletion (CADD) (score 26.7), inherited from the mother; (II) c.390del (p.Glu131Argfs*12) in exon 2, a known frameshift classified as likely pathogenic, inherited from the father. Both variants reside on opposite alleles, satisfying autosomal-recessive inheritance. After 4 weeks of oral magnesium oxide (600 mg bid) and spironolactone 25 mg od, serum K+ rose to 3.5 mmol/L, Mg2+ to 0.70 mmol/L and BP normalised (124/78 mmHg) without anti-hypertensives.
CONCLUSIONS: We describe the first GS patient harbouring the novel c.254C>T (p.Thr85Ile) variant who presented with overt hypertension. The findings expand the mutational spectrum of SLC12A3 and underscore that hypertension does not exclude GS. Functional validation of p.Thr85Ile is warranted to confirm its pathogenicity.
CASE DESCRIPTION: A 19-year-old man was admitted for progressive polyuria, constipation, proximal muscle weakness and fatigue lasting 6 weeks. Laboratory tests showed hypokalaemia (K+ 2.4 mmol/L), hypomagnesaemia (Mg2+ 0.48 mmol/L), hypochloraemia (Cl- 96 mmol/L), hypocalciuria (Ca2+/Cr 0.07 mmol/mmoL) and hyper-reninaemia (plasma renin 52 ng/mL/h; aldosterone 380 pg/mL), together with a paradoxical elevated blood pressure (BP) (152/98 mmHg on three occasions, no medication). Renal ultrasound was normal; 24-h urinary Na+ 210 mmol, K+ 68 mmol, Ca2+ 0.8 mmol. Targeted next-generation sequencing of SLC12A3 disclosed compound-heterozygous variants: (I) c.254C>T (p.Thr85Ile) in exon 1, absent from gnomAD and ClinVar, predicted deleterious by SIFT, PolyPhen-2 and Combined Annotation Dependent Depletion (CADD) (score 26.7), inherited from the mother; (II) c.390del (p.Glu131Argfs*12) in exon 2, a known frameshift classified as likely pathogenic, inherited from the father. Both variants reside on opposite alleles, satisfying autosomal-recessive inheritance. After 4 weeks of oral magnesium oxide (600 mg bid) and spironolactone 25 mg od, serum K+ rose to 3.5 mmol/L, Mg2+ to 0.70 mmol/L and BP normalised (124/78 mmHg) without anti-hypertensives.
CONCLUSIONS: We describe the first GS patient harbouring the novel c.254C>T (p.Thr85Ile) variant who presented with overt hypertension. The findings expand the mutational spectrum of SLC12A3 and underscore that hypertension does not exclude GS. Functional validation of p.Thr85Ile is warranted to confirm its pathogenicity.