Table 2.
Congenital causes of hypomagnesemia
| Sources of magnesium loss | Sites of defect in magnesium metabolism | Congenital | |
|---|---|---|---|
| Gastro-intestinal absorption | Passive reabsorption | ||
| Active reabsorption | TRPM6 | Hypomagnesemia with secondary hypocalcemia | |
| Cellular shift; tissue sequestration | – | – | |
| Kidney handling | Glomerular filtration | – | |
| Proximal tubular reabsorption | Proximal renal tubular acidosis with or without associated Fanconi’s syndrome | ||
| Thick ascending limb of loop of Henle | Claudin-16 | Familial hypomagnesemia with hypercalciuria, and nephrocalcinosis | |
| Claudin-19 | Familial hypomagnesemia, with hypercalciuria, nephrocalcinosis, and ocular manifestation | ||
| NKCC2 | Antenatal Bartter syndrome type 1 with low-normal serum magnesium | ||
| ROMK | Antenatal Bartter syndrome type II with low-normal serum magnesium | ||
| ClC-Kb | Classic Bartter syndrome type III, hypomagnesemia in 20% | ||
| CaSR | Bartter syndrome type V | ||
| Distal convoluted tubule: | TRPM6 | Hypomagnesemia, secondary hypocalcemia | |
| Apical regulators/effectors of TRPM6 | |||
| Kv1.1 | Isolated autosomal dominant hypomagnesemia | ||
| Kir4.1/Kir5.1 | Kir4.1 mutation: SeSAME/EAST syndrome; Kir5.1 mutation: hypomagnesemia, hypokalemia, hyperchloremic metabolic acidosis and hypercalciuria | ||
| NCCT | Gitelman syndrome | ||
| Basolateral regulators/effectors of TRPM6 | |||
| Na+-K+-ATPase | FXYD2: autosomal dominant hypomagnesemia with hypocalciuria; HNF1B: renal cysts and diabetes mellitus with renal magnesium wasting and hypocalciuria | ||
| EGF | Isolated recessive hypomagnesemia with normocalciuria | ||
| CaSR | Activating mutations | ||
| CNNM2 | Autosomal dominant hypomagnesemia | ||
| Hormonal regulators of TRPM6 | |||
| Insulin | TRPM6 polymorphisms Ile1393Val and Lys1584Glu: reduced insulin activation of TRPM6, particularly if low dietary magnesium intake; tendency for diabetes mellitus | ||
| Other sources of loss | Nonspecific tubular injury/cellular leak | – | |
| Other | – | ||
Abbreviations: NKCC2, sodium potassium 2 chloride cotransporter; ROMK, renal outer medullary potassium channel; ClC-Kb, chloride channel Kb; CaSR, calcium sensing receptor; Kv1.1, potassium voltage-gated channel subfamily A member 1; Kir4.1/Kir5.1, inward-rectifier type potassium channel 4.1/5.1 dimer; NCCT, sodium chloride cotransporter; Na+-K+-ATPase, sodium-potassium adenosine triphosphatase; HNF1B, hepatocyte nuclear factor 1 homeobox B; EGF, epidermal growth factor; CNNM2, cyclin M2; TPRM 6, transient receptor potential melastatin 6; SeSAME/EAST syndrome, SEizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte imbalance Epilepsy, Ataxia, Sensorineural deafness, and renal Tubulopathy.