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

Abstract

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.

Gitelman syndrome combined with diabetes mellitus: A case report and literature review

“…Notably, certain individuals may remain asymptomatic, often leading to misdiagnoses as sporadic hypokalemia or hypomagnesemia. [ 3 ] Nonetheless, Severe adverse events have also been reported in the literature, encompassing growth retardation, [ 2 , 4 ] chondrocalcinosis, [ 5 ] generalized seizures, [ 6 , 7 ] non-periodic paralysis, [ 2 ] rhabdomyolysis, [ 8 ] and even cardiac arrest. [ 9 ] The course of GS typically follows a mild trajectory, characterized by predominantly modest clinical symptoms.…”

Molecular diagnosis of adult patients with clinically unexplained hypokalemia without hypertension demonstrated a diagnostic yield of 30.5%

“…For example, in addition to a high potassium diet and supplementation, treatment of GS included liberal salt intake, magnesium supplementation, and the use of potassium‐sparing diuretics or renin‐angiotensin‐system blockers, in contrast to the low sodium/carbohydrate diets and carbonic anhydrase inhibitors in HypoPP. In GS, long‐term consequences, such as chronic kidney disease, chondrocalcinosis, 9 sclerochoroidal calcifications, 10 and decreased rate of bone remodeling, 11 need to be considered. However, myopathy and long‐lasting interictal muscle weakness might occur in some patients with HypoPP 6,12 .…”

A novel mutation of SLC12A3 gene causing Gitelman syndrome

“… 2 Many new mutations of the SLC12A3 gene have been reported recently. 4 – 11 We are presenting a patient who was evaluated for hypokalemia and was found to have a novel mutation of the SLC12A3 gene.…”