From the Guidelines
DiGeorge syndrome causes hypocalcemia primarily due to hypoparathyroidism, which is a result of the underdevelopment or absence of the parathyroid glands. This condition, also known as 22q11.2 deletion syndrome, involves the deletion of genetic material from chromosome 22 during embryonic development, leading to various complications, including endocrine issues 1. The parathyroid glands, which normally develop from the third and fourth pharyngeal pouches, fail to form properly or are completely absent, resulting in a deficiency of parathyroid hormone (PTH). PTH is crucial for maintaining calcium homeostasis by increasing calcium reabsorption in the kidneys, promoting calcium absorption in the intestines through vitamin D activation, and stimulating bone resorption to release calcium into the bloodstream. Without adequate PTH, calcium levels drop, leading to hypocalcemia.
Some key points to consider in the management of hypocalcemia in DiGeorge syndrome include:
- Regular investigations, including measurements of pH-corrected ionized calcium, magnesium, parathyroid hormone, and creatinine concentrations, are recommended 1.
- Daily calcium and vitamin D supplementation are recommended for all adults with 22q11.2DS, with targeted monitoring of calcium concentrations at vulnerable times, such as peri-operatively, perinatally, or during severe illness 1.
- Treatment with hormonally active metabolites of vitamin D, such as calcitriol, may be necessary for more severe hypocalcemia, but requires consultation with an endocrinologist 1.
- Caution is advised with respect to over-correction, which can result in iatrogenic hypercalcemia, renal calculi, and renal failure 1.
It is essential to note that hypocalcemia in DiGeorge syndrome can be associated with various symptoms, including fatigue, emotional irritability, abnormal involuntary movements, seizures, and cardiac arrhythmias, and may predispose to osteopenia/osteoporosis 1. Therefore, early diagnosis and treatment of hypocalcemia are crucial to prevent these complications and improve the quality of life for individuals with DiGeorge syndrome.
From the Research
Causes of Hypocalcemia in DiGeorge Syndrome
- DiGeorge syndrome is characterized by hypocalcemia due to hypoparathyroidism, which results from the abnormal development of the third and fourth pharyngeal pouches during embryonic life 2.
- The syndrome is caused by a chromosomal microdeletion at 22q11.2, leading to impaired development of the pharyngeal pouch system, including the parathyroid glands 3.
- The parathyroid hypoplasia caused by DiGeorge syndrome results in a disturbance in calcium regulation, leading to hypocalcemia 4.
Relationship between Hypocalcemia and Congenital Heart Disease
- Hypocalcemia is more frequently identified in patients with 22q11.2 deletion syndrome (22q11.2DS) and congenital heart disease (CHD) 5.
- The frequency of diagnosed hypocalcemia is greater in patients with 22q11.2DS and CHD compared to those without CHD, with 62.36% of patients with CHD having a history of hypocalcemia 5.
- The age of onset of hypocalcemia is also affected, with 66.47% of patients with CHD and hypocalcemia experiencing neonatal/infantile hypocalcemia 5.
Clinical Presentation of Hypocalcemia in DiGeorge Syndrome
- Hypocalcemia can present with seizures, as seen in a patient with DiGeorge syndrome who developed hypocalcemia-induced seizures at the age of 40 4.
- The patient's calcium concentration was 5.5mg/dL, and the level of intact parathyroid hormone (PTH) was 6 pg/mL, indicating hypoparathyroidism 4.
- Hypocalcemia is a cardinal feature of DiGeorge syndrome, and its diagnosis is important for disease management and genetic counseling 3.