Hypomagnesemia with secondary hypocalcemia
Hypomagnesemia with secondary hypocalcemia | |
---|---|
Other names | Familial primary hypomagnesemia with hypocalcuria |
Specialty | Endocrinology |
Hypomagnesemia with secondary hypocalcemia (HSH) is an
One of the main symptoms of HSH is the occurrence of
Pathophysiology
HSH is primarily caused by a reduction in intestinal magnesium reabsorption. Intestinal magnesium reabsorption primarily occurs by
More than 30 mutations in the TRPM6 gene have been identified as being associated with HSH. These mutations are scattered throughout the gene (refer to Table 1). Out of the eight HSH mutations that have been tested, none have been shown to produce whole-cell current. One notable missense mutation, S141L, inhibits coassembly with TRPM7, as well as other TRPM6 subunits, and fails to allow traffic of the channel to the cell membrane. The trafficking ability and coassembly of other mutant forms of TRPM6 have yet to be extensively studied and require further investigation.[citation needed]
While hypomagnesemia in patients with HSH directly results from TRPM6 mutations, hypocalcemia is an indirect and secondary consequence. Decreased serum magnesium levels result to reduced the secretion of parathyroid hormone (PTH) by the parathyroid gland. PTH plays a vital role in regulating serum calcium levels. Decreased levels of PTH result in a decrease in the availability of calcium in the bloodstream, which contributes to the neurological symptoms observed in HSH.[citation needed]
Mutation | Location | Functional? | Reference | |
---|---|---|---|---|
Nucleotide | Amino acid | |||
c.C166T | R56X | N-terminus | [2] | |
c.C422T | S141L | N-terminus | No | [3],[4],[5],[6] |
c.G469T | E157X | N-terminus | [5] | |
c.T521G | I174R | N-terminus | [7] | |
c.668delA | D223fsX263 | N-terminus | [5] | |
c.1010+5G→C | Splicing | N-terminus | [2] | |
c.A1060C | T354P | N-terminus | [7] | |
c.1134+5G→A | Splicing | N-terminus | [7] | |
c.1208-1G→A | Splicing | N-terminus | [5] | |
c.1280delA | H427fsX429 | N-terminus | No | [3],[5] |
c.1308+1G→A | Splicing | N-terminus | [5] | |
c.C1437A | Y479X | N-terminus | [7] | |
c.C1450T | R484X | N-terminus | [2] | |
c.C1769G | S590X | N-terminus | No | [3],[5],[8] |
c.del1796-1797 | P599fsX609 | N-terminus | [5] | |
c.2009+1G→A | Splicing | N-terminus | [2],[7] | |
c.G2120A | C707Y | N-terminus | [7] | |
c.2207delG | R736fsX737 | N-terminus | No | [3],[5],[8] |
c.2537-2A→T | Splicing | N-terminus | [5] | |
c.2667+1G→A | Splicing | [3],[5] | ||
c.C2782T | R928X | M3 | No | [5] |
c.del Ex 21 | M4 | [5] | ||
c.Del2831-2832insG | I944fsX959 | M4-M5 | [5] | |
c.3209-68A→G | Splicing | [2] | ||
c.del Ex 22 + 23 | M5-6 | [5] | ||
C.3537-1G→A | Splicing | [3],[5] | ||
c.3779-91del | Q1260fsX1283 | C-terminus | [3],[5] | |
c.del Ex 25 - 27 | C-terminus | [5] | ||
c.del Ex 26 | Y1533X | C-terminus | No | [5] |
c.5017-18delT | L1673fsX1675 | C-terminus | No | [5] |
c.del Ex 31 + 32 | C-terminus | No | [5] | |
c.5057+2T→C | Splicing | C-terminus | [5] | |
c.A5775G | Splicing | C-terminus | [5] |
Diagnosis
Diagnosis typically occurs during the first six months of life due to the characteristic neurological symptoms. These symptoms include
Treatment
Treatment of HSH involves administration of high doses of magnesium salts. These salts may be taken orally or otherwise (e.g. subcutaneously). This treatment works by increasing magnesium absorption through the non-TRPM6 mediated paracellular transport pathways. This treatment must be continued throughout life.[citation needed]
History
HSH was originally believed to be an
See also
- Bartter's syndrome
- Gitelman syndrome
- Hypomagnesemia
- Hypocalcemia
References
- Konrad M, Schlingmann K, Gudermann T (2004). "Insights into the molecular nature of magnesium homeostasis". Am J Physiol Renal Physiol. 286 (4): F599–605. PMID 15001450.