Congenital Magnesium Malabsorption - Types, Symptoms, and Treatment

Introduction

Magnesium is the fourth most prevalent cation in the body and the second most abundant cation within the cells. Magnesium is essential for numerous physiological processes of several organs, including the cardiovascular and neuromuscular systems and the synthesis of proteins and nucleic acids for intermediate metabolism. The mechanism of action depends on two key factors: its capacity to form chelates with significant intracellular anionic ligands, particularly ATP (adenosine triphosphate), and its capacity to outcompete calcium for binding sites on proteins and membranes. Magnesium aids in maintaining a low resting intracellular free calcium ion concentration, which is essential for many cellular activities, by competing with membrane binding sites and encouraging calcium sequestration by the sarcoplasmic reticulum. Magnesium also impacts the permeability, electrical characteristics of membranes, and the tone of the smooth muscles of the blood vessels. Numerous other vital biological activities, such as cellular energy metabolism, depend on magnesium.

What Is Congenital Magnesium Malabsorption?

Magnesium deficiency and hypomagnesemia are when the entire body's magnesium depletion occurs with normal blood magnesium concentrations. An uncommon condition called congenital hypomagnesemia affects brain and nervous system development. Hypomagnesaemia is more common in individuals with other electrolyte disorders, like in patients with hypokalemia (low serum potassium concentrations), hypophosphatemia (reduced phosphate level), hyponatremia (reduced sodium level), and hypocalcemia (reduced calcium level). Patients receiving intensive care are at a high risk of hypomagnesemia, which is linked to higher mortality. However, calcium and magnesium supplements restore the levels of phosphatemia and magnesium but not the levels of calcemia.

What Are the Causes of Congenital Magnesium Malabsorption?

Hypomagnesemia can be brought on by either the gastrointestinal tract or the kidneys. Due to the slow interchange of extracellular magnesium with the bone and cell, hypomagnesemia develops with a moderate magnesium shortage, regardless of the source. It is also accompanied by the congenital disorder of renal tubular reabsorption of magnesium and is mainly due to mutation of CLDN16, CLDN19, CASR, CLCNKB, SLC12A3, BSND, KCNJ10, FXYD2, HNF1B, PCBD1, MT-TI, SARS2 and TRPM6.

What Is the Classification of Congenital Magnesium Malabsorption?

Congenital or inherited magnesium malabsorption is widely classified into six types based on the gene mutation:

• Classic Bartter Syndrome: It gets manifested in infants with decreased serum magnesium and potassium levels without renal stone or nephrocalcinosis (calcium deposition in the kidney). However, the level of serum calcium remains normal.

• Antenatal Bartter’s Syndrome: It is similar to classic Bartter syndrome but with the presence of nephrocalcinosis.

• Gitelman-Like Hypomagnesemia: Increased urine calcium concentration abruptly reduces serum magnesium and potassium levels.

• Isolated Dominant Hypomagnesemia: It is frequently seen in children with decreased serum magnesium and urine calcium level.

• Familial Hypomagnesemia: Reduction in rate of serum magnesium, with increase in the concentration of calcium and magnesium in urine.

• Hypomagnesemia With Secondary Hypocalcemia: An hereditary illness known as hypomagnesemia with subsequent hypocalcemia is brought on by the body's inability to absorb and store magnesium from food. As a result, the blood's magnesium levels are incredibly low (hypomagnesemia).

What Are the Clinical Manifestations of Magnesium Malabsorption or Hypomagnesemia?

Many people with hypomagnesemia and magnesium insufficiency are asymptomatic (shows no symptoms). Rather than the blood magnesium content, symptoms may depend more on the rate of development of magnesium shortage and total deficiency in the body. Magnesium deficiency symptoms and signs typically only appear once serum magnesium levels drop to 0.5 mmol/L (millimoles per litre) or below. The major clinical manifestation of magnesium deficiency include:

• Hypokalaemia (potassium levels of the body less than 2.5 mEq/L).

• Hypocalcaemia (decreased level of blood calcium).

• Carpopedal spasm (painful involuntary muscle contractions in the hands and feet).

• Convulsions (uncontrolled shaking of the body and limb movement).

• Muscular cramps.

• Muscular weakness and tremors.

• Vertigo or dizziness.

• Nystagmus (rapid eye movement).

• Depression and psychosis.

• Athetoid movements (a slow, continuous, involuntary twisting movement that prevents maintenance of a stable posture) and choreiform movements (random-appearing involuntary movements).

• Atrial tachycardias (abnormal heart rhythm).

• Supraventricular arrhythmias (irregularly fast heartbeat).

• Ventricular arrhythmias (irregular cardiac rhythms that cause your heart's lower chambers to delay pulses rather than pump blood).

• Digoxin sensitivity (hypercalcemia, hypokalemia, and hypomagnesemia enhance digoxin sensitivity).

• Hypertension.

• Myocardial infarction (heart attack).

• Osteoporosis (a bone condition that appears when bone mass and mineral density diminish or when the composition and strength of bone significantly change).

• Migraine.

• Asthma.

• Chronic fatigue syndrome.

• Impaired athletic performance.

What Is the Treatment of Hypomagnesemia?

It is hard to determine the exact degree of magnesium insufficiency. Magnesium should be administered to patients who exhibit the signs and symptoms of a magnesium shortage as soon as possible. It cannot be replaced orally in symptomatic individuals because it is poorly absorbed and, in high doses, produces adverse gastrointestinal effects.

It has been suggested that eight mmol of magnesium should be administered as magnesium sulfate over one minute, followed by 40 mmol of magnesium over the course of the following five hours, in severely sick individuals who exhibit ventricular tachycardia or convulsions. Over the course of the following 10 hours, an additional 40 mmol may be given if required. In fewer emergency conditions, continuous intravenous infusions of 0.5 mmol/Kg/24 hour or intramuscular injections of 4 mmol (2 mls of 50 % magnesium sulfate) every three to four hours for the first day may be administered.

The first step in treating magnesium shortage symptoms is to increase the amount of magnesium in your diet. Rich nutrient food sources include:

• Greens.

• Dry beans.

• Nuts.

• Seeds.

• Whole gains.

• Mango.

• Avocado.

• Black bean salad.

Above mentioned diets that are rich in magnesium can be used to treat mild asymptomatic hypomagnesemia. Oral magnesium supplementation may be necessary in cases of chronic magnesium depletion. Only magnesium gluconate is advised for magnesium supplementation since it is better absorbed. It produces less diarrhea, even though magnesium is also available in sulfates, lactates, hydroxides, oxides, and chlorides.

Conclusion:

Hospital patients typically have disorders of magnesium metabolism, which are usually undetected. Numerous illnesses, including diabetes, cardiovascular disease, and osteoporosis, may be exacerbated by low magnesium consumption. Cardiac arrhythmias and hypocalcemia are frequent side effects of hypomagnesemia. Even though it happens less frequently, to prevent these problems, it is essential to identify magnesium metabolism disorders as soon as possible and to rectify the electrolyte imbalance.