Disorders of Magnesium Metabolism

Magnesium (Mg) is essential for all enzyme processes involving adenosine triphosphate (ATP) and many enzymes involved in nucleic acid metabolism. It is required for thiamine metabolism, appears to stabilise the structure of DNA and RNA and is in some way related to calcium and potassium metabolism. The genetic mechanisms which control magnesium homeostasis are currently being researched.^1,2
It is involved in hormone production (most notably parathyroid hormone) and is implicated in neurotransmission. Changes in normal levels can thus have wide-sweeping effects on body function.^3,4

Magnesium is the 4th commonest cation found in the body. Most is sequestered in bone cells, with only about 1% in the extra-cellular fluid. Normal plasma Mg concentration ranges from 0.70 to 1.05 mmol/l.

Plasma concentration is a reflection of the dietary intake of magnesium, and of the ability of the kidneys and gastrointestinal tract to retain it. Because most magnesium is found intracellularly, the relationship between total body deficiency and plasma concentration is poor. However, in cases of severe deficiency, a reduction in plasma concentration can be seen.

This is defined as a level less than 0.7mmol/l. It may be seen in:

• Malabsorption syndromes⁵
• Protein-calorie malnutrition
• Disorders of the parathyroid gland⁶
• Chronic alcoholism⁷
• Chronic diarrhoea
• Patients on long-term proton pump inhibitors⁸

Presentation of hypomagnesaemia⁴

This may present with:

• Loss of appetite
• Vomiting
• Tiredness
• Weakness
• Personality change
• Tetany
• Tremor
• Muscle fasciculations

Investigations for hypomagnesaemia⁴

• Serum magnesium should be arranged although it should be borne in mind that the level may be normal in early mild deficiency.
• Protein loss may affect the reading, as the majority of extracellular magnesium is protein-bound.
• Magnesium deficiency may be associated with hypocalcaemia, hypophosphataemia and hypokalaemia, so calcium, phosphate and potassium levels should all be checked.
• ECG changes are non-specific but may include include ST segment depression; tall, peaked T waves; flat T waves or depression in the precordium; U waves; loss of voltage; PR prolongation; and widened QRS.

Hypomagnesaemia management⁴

• Mild symptoms usually respond to oral replacement therapy with a magnesium salt (e.g. magnesium gluconate 500 mg/day = 27 mg elemental magnesium - orally for adults. Child dose is 3-6 mg elemental magnesium/kg/day orally).
• Severe depletion will require intravenous replacement with magnesium sulfate, 2-4 g of 50% solution (8.3-16.6mmol) diluted in saline or dextrose intravenously (IV) over 30-60 min for adults: 0.5mmol/kg IV on day 1; 0.25 mmol/kg/d over next 3 days for children.
• 24 hour urinary magnesium excretion should be monitored to ensure response to treatment.
• Secondary causes should be treated, and oral replacement continued if the cause cannot be corrected.

This is much less common that Hypomagnesaemia. It is most frequently encountered in patients with renal failure taking drugs containing magnesium¹¹ and in patients on parenteral nutrition.¹⁰ It is also occasionally seen after prolonged laxative use.¹²

Presentation of hypermagnesaemia⁹

The first changes (at 2.3-5.0 mmol/l). may be noted on an ECG and include depression of sinoatrial node activity and sometimes atrial fibrillation.
At higher levels the following may occur:

• Disappearance of deep tendon reflexes
• Hypotension
• Respiratory depression
• Narcosis
• Parkinson-like symptoms
• Psychological changes
• Seizures (rare)
• Cardiac arrest (at > 6.0-7.5 mmol/l)

Investigations for hypermagnesaemia⁹

• Atomic absorbance spectrophotometry (AAS) is the most specific technique available for measuring total serum magnesium.¹³
• Hyperkalaemia and hypercalcaemia are often present, and these levels should also be checked.
• ECG changes are non-specific but may include prolongation of the P-R interval and intraventricular conduction delay.

Hypermagnesaemia management⁹

• Hypermagnesaemia can be corrected using intravenous calcium. Calcium chloride (5 ml of a 10% solution) should be given IV over 30 seconds. The patient should be treated in an intensive care unit with regular ECG monitoring.
• If the patient has a normal urine output and renal function, magnesium loss can be enhanced using intravenous saline infusions and furosemide diuresis.
• Dialysis for may be used for patients with:
  • Renal insufficiency .
  • Severe asymptomatic hypermagnesaemia (>4 mmol/l).
  • Serious cardiovascular or neuromuscular symptoms irrespective of serum magnesium level.
• Non-magnesium containing enemas may be used to enhance gastrointestinal loss.
• On discharge, the patient's ongoing medication regime should be reviewed to ensure that it does not include magnesium-containing laxatives or antacids.