OVERVIEW

What is hereditary hypomagnesemia?

Hereditary hypomagnesemia is a rare genetic disorder characterized by low blood magnesium levels, with or without other electrolyte abnormalities. Magnesium ions play a crucial role in various biochemical reactions, including nerve conduction, potassium and calcium transport, and muscle function.

Treatment primarily involves oral magnesium supplements and supportive care, but the condition cannot be cured. Without treatment, patients may experience seizures or impaired consciousness due to magnesium deficiency. Active management can effectively alleviate symptoms.

Is hereditary hypomagnesemia common?

No, it is rare. In 2018, hereditary hypomagnesemia was included in China's First List of Rare Diseases jointly issued by the National Health Commission and four other government departments.

What are the types of hereditary hypomagnesemia?

Based on causative genes and inheritance patterns, it is classified into several types:

• Gitelman syndrome;
• Familial hypomagnesemia with hypercalciuria and nephrocalcinosis;
• Familial hypomagnesemia with secondary hypocalcemia;
• Autosomal dominant hypomagnesemia with hypocalciuria;
• Isolated autosomal recessive hypomagnesemia.

SYMPTOMS

What are the common manifestations of hereditary hypomagnesemia?

The clinical manifestations of different types of hereditary hypomagnesemia vary, but all may exhibit symptoms caused by low blood magnesium, hypokalemia, hypocalcemia, etc.

• Neuromuscular system: Hypomagnesemia can lead to neurological abnormalities, such as generalized convulsions, coma, and incoordination of limb movements. It may also cause tremors, tetany, and muscle weakness.

• Cardiovascular system: Mainly manifests as changes in electrocardiogram (ECG), including widened QRS complex and prolonged PR interval. Severe cases may lead to arrhythmias, presenting as chest tightness, palpitations, or even sudden death.

• Urinary system: May cause kidney stones and renal insufficiency.

• Skeletal system: Hypomagnesemia can lead to chondrocalcinosis, while hypocalcemia may result in osteomalacia.

• Digestive system: Hypomagnesemia can induce intestinal obstruction.

• Endocrine system: May be accompanied by diabetes.

What are the consequences of hereditary hypomagnesemia?

If the condition manifests during the neonatal or infantile period, the disease is often severe with a poor prognosis. Without timely treatment, affected children may experience significant developmental delays or even face life-threatening risks.

CAUSES

What Causes Hereditary Hypomagnesemia?

The primary cause is defects in the genes regulating renal magnesium reabsorption, leading to excessive urinary excretion of magnesium ions.

Different types of hereditary hypomagnesemia involve distinct pathogenic genes.

• Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: Caused by mutations in the CLDN16 gene on chromosome 3q27-q29.

• Familial hypomagnesemia with secondary hypocalcemia: Results from mutations in the TRPM6 gene on chromosome 9q22.

• Gitelman syndrome: Caused by mutations in the SLC12A3 gene on chromosome 16q13.

Who Is Prone to Hereditary Hypomagnesemia?

This is a rare disease, with Gitelman syndrome being the most common type, affecting 1/40,000 to 10/40,000 individuals, with no gender differences.

DIAGNOSIS

What tests are needed for hereditary hypomagnesemia?

• Genetic testing: This is the gold standard for diagnosing hereditary hypomagnesemia. It helps identify the pathogenic gene and determine the specific subtype of hereditary hypomagnesemia.

• Blood electrolyte tests: Including potassium, magnesium, calcium, phosphorus, blood gas, and blood glucose. These tests determine the levels of magnesium and other electrolytes in the blood.

• Urine electrolyte tests: These can determine whether magnesium deficiency is renal in origin and help rule out other conditions.

• Head CT or MRI: These can help detect intracranial space-occupying lesions or other disorders.

• Electrocardiogram (ECG): This assesses whether the patient has arrhythmias.

• Renal ultrasound: This evaluates the kidneys for stones or cysts.

• Hydrochlorothiazide test: For patients suspected of having Gitelman syndrome, this test can confirm the diagnosis.

Which diseases are easily confused with hereditary hypomagnesemia?

• Non-renal magnesium deficiency: Includes reduced intake (e.g., fasting), vomiting, diarrhea, and short bowel syndrome, all of which can lead to hypomagnesemia.

• Secondary renal magnesium deficiency: Conditions such as long-term use of thiazide diuretics, alcoholism, and hypercalcemia can increase renal magnesium excretion. Blood and urine tests, immunological tests, renal biopsy, and genetic testing can help differentiate these conditions.

TREATMENT

Which department should I visit for hereditary hypomagnesemia?

Endocrinology or pediatrics.

How to provide first aid during an episode of hereditary hypomagnesemia?

Patients with hereditary hypomagnesemia who experience severe magnesium deficiency, especially if accompanied by generalized convulsions, impaired consciousness, or arrhythmias, require emergency treatment. Call 120 immediately and accurately describe the patient's condition.

Patients with mild to moderate hypomagnesemia can be given oral magnesium supplements immediately, such as magnesium oxide.

How is hereditary hypomagnesemia treated?

The treatment of hereditary hypomagnesemia focuses on symptomatic and supportive care, maintaining electrolyte balance, and preventing severe complications.

• Replacement therapy: Magnesium can be supplemented orally with potassium magnesium aspartate, 25% magnesium sulfate solution, or magnesium chloride. In more severe or urgent cases, intravenous magnesium infusion may be considered. Infusion must be administered slowly while monitoring tendon reflexes and serum magnesium levels to avoid magnesium toxicity.

• Symptomatic treatment: Includes managing convulsions, urinary tract stones, and infections. If kidney dysfunction occurs, corresponding treatment is necessary.

Can hereditary hypomagnesemia be cured?

Hereditary hypomagnesemia currently has no cure and requires lifelong medication. Gene editing therapy is the only potential curative approach, but further research is needed.

With active replacement and symptomatic treatment, patients' symptoms can be significantly alleviated. Gitelman syndrome generally has favorable treatment outcomes, but other types of hereditary hypomagnesemia are prone to recurrent episodes.

Is regular follow-up necessary for hereditary hypomagnesemia?

Yes, follow up as advised by your doctor.

DIET & LIFESTYLE

What should patients with hereditary hypomagnesemia pay attention to in their diet?

Patients need to consume more magnesium-rich foods such as grains, seafood, and fruits. In addition, they should eat more seaweed, sesame seeds, and mushrooms. Quit smoking and drinking, and avoid stimulant beverages like coffee.

What should patients with hereditary hypomagnesemia pay attention to in daily life?

• Newborns are recommended to be breastfed, with supplementation of water and electrolytes;

• Strictly follow the doctor's instructions, take medication on time and in the prescribed dosage, and do not stop medication without authorization;

• Schedule regular check-ups to monitor the condition and potential side effects of medications;

• Patients and their families should learn about hereditary hypomagnesemia to recognize worsening symptoms promptly and seek immediate medical attention.

How to care for patients with hereditary hypomagnesemia?

Encourage patients to consume more magnesium-rich foods while ensuring regular medication use and timely follow-up examinations. If symptoms such as generalized convulsions, impaired consciousness, or arrhythmia occur, the patient should be sent to the hospital immediately for treatment.

PREVENTION

Can hereditary hypomagnesemia be prevented?

Individuals with a family history of hereditary hypomagnesemia should undergo family genetic screening, genetic counseling, and prenatal diagnosis to promote eugenics and better birth outcomes.