A rare case of Gitelman’s syndrome presenting with hypocalcemia and osteopenia

Abstract

Gitelman's syndrome (GS), an autosomal recessive disorder caused by a defect of the thiazide-sensitive Na-Cl cotransporter (TSC) at the distal tubule, is characterized by hyperreninemic hyperaldosteronism with normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria. An 18-yr-old Japanese man was admitted to our hospital with a history of muscle weakness and transient tetanic episodes. He showed hypocalcemia in addition to hypokalemia, severe hypomagnesemia, hypocalciuria and hyperreninemic hyperaldosteronism with normal blood pressure. Furthermore, bone mineral density at the lumbar spine revealed osteopenia. A diagnosis of GS was made on the basis of clinical features, laboratory data and renal function test. The electrolyte imbalance was corrected and bone mineral density was slightly increased with chronic treatment of magnesium and potassium salts. Genetic analysis revealed that TSC gene of the patient has a heterozygous C to A nucleotide substitution at position 545 in exon 4, which causes a threonine (Thr) to lysine (Lys) substitution at position 180. This is a rare case of GS with hypocalcemia and osteopenia which could be caused by severe hypomagnesemia.

Problems in diagnosing atypical Gitelman’s syndrome presenting with normomagnesaemia

“…Although TSC in patient 2 had a homozygous missense mutation (Arg642Lys), patient 1 had a heterozygous missense mutation (Thr180Lys). We speculate that patient 1 may have an unidentified gene abnormality on the allele in addition to the Thr180Lys mutation 9 . The functional consequence of the mutation in patient 3 is unknown, however it may be speculated that this mutation might change amino acid residues due to alternative initiation of translation at a second, in‐frame ATG present 53 codons downstream, potentially impairing the function of the TSC protein 11 .…”

“…We speculate that patient 1 may have an unidentified gene abnormality on the allele in addition to the Thr180Lys mutation. 9 The functional consequence of the mutation in patient 3 is unknown, however it may be speculated that this mutation might change amino acid residues due to alternative initiation of translation at a second, in-frame ATG present 53 codons downstream, potentially impairing the function of the TSC protein. 11 Patients 4 and 5 were compound heterozygous for two different mutations on both TSC alleles, which is the most common inheritance pattern in GS patients.…”

“…This study included five patients (four males and one female) with hypokalaemia from Hokkaido University Hospital, Sapporo Shakai Hoken General Hospital, Sapporo City Hospital, Takikawa City Hospital in Hokkaido, and Yokohama City University Hospital in Yokohama, Japan. The details of two males and one female (patients 1, 2 and 3) were described previously 9–11 . All five patients were on normal diets and not taking either regular medications or supplements that could affect serum electrolytes.…”

“…The details of two males and one female (patients 1, 2 and 3) were described previously. [9][10][11] All five patients were on normal diets and not taking either regular medications or supplements that could affect serum electrolytes. Serum and urinary electrolytes, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured by standard laboratory techniques.…”

Severe Hyponatremia and Hypocalcemia in Gitelman Syndrome: A Case Report

“…Pantanetti et al [8] and Nakamura et al [9] describe two patients with GS in whom hypocalcemia developed due to hypomagnesemia. The combination of two rare complications, namely hyponatremia and hypocalcemia, in our case …”