Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene

• Published in: Reumatismo Vol. 72; no. 1; pp. 67 - 70
• Main Authors: Conticini, E, Negro, A, Magnani, L, Ugolini, R, Atienza-Mateo, B, Frediani, B, Salvarani, C
• Format: Journal Article
• Language: English; Italian
• Published: Italy PAGEPress Publications 10.04.2020
• Subjects: Aged; chondrocalcinosis; Chondrocalcinosis - complications; Electromyography; Furosemide - administration & dosage; Gitelman; Gitelman Syndrome - complications; Gitelman Syndrome - diagnosis; Gitelman Syndrome - genetics; Glycyrrhiza - adverse effects; Humans; Hypercalciuria - complications; Male; Mutation; Nephrocalcinosis - complications; Nervous System Diseases - complications; Nervous System Diseases - diagnosis; neuropathy; Renal Tubular Transport, Inborn Errors - complications; Sodium Potassium Chloride Symporter Inhibitors - administration & dosage; Solute Carrier Family 12, Member 3 - genetics; tubulopathy
• ISSN: 0048-7449; 2240-2683
• DOI: 10.4081/reumatismo.2020.1255

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.