From the Guidelines
Hypocalcemia in DiGeorge syndrome occurs primarily due to hypoparathyroidism, which is typically attributable to the underdevelopment or absence of the parathyroid glands. During embryonic development, the parathyroid glands form from the third and fourth pharyngeal pouches, which are affected by the genetic deletion (typically on chromosome 22q11.2) characteristic of DiGeorge syndrome 1. Without properly functioning parathyroid glands, patients cannot produce adequate amounts of parathyroid hormone (PTH), which normally increases serum calcium levels by enhancing bone resorption, increasing calcium reabsorption in the kidneys, and promoting vitamin D activation to increase intestinal calcium absorption. This PTH deficiency leads to hypocalcemia, which can manifest as tetany, seizures, or cardiac abnormalities.
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 magnesium supplementation for those with hypomagnesemia 1.
- Treatment with hormonally active metabolites of vitamin D for more severe hypocalcemia usually requires consultation with an endocrinologist 1.
- Targeted monitoring of calcium concentrations should be considered at vulnerable times, for example, peri-operatively, perinatally, or during severe illness 1.
- Caution is advised with respect to over-correction, which can result in iatrogenic hypercalcemia, renal calculi, and renal failure 1.
It's also important to note that other conditions, such as hypothyroidism and hypomagnesemia, may be associated with hypocalcemia in DiGeorge syndrome, and should be considered in the diagnostic workup and management plan 1.
Overall, the management of hypocalcemia in DiGeorge syndrome requires a comprehensive approach that takes into account the underlying pathophysiology of the condition, as well as the potential for associated complications and comorbidities.
From the Research
Mechanism of Hypocalcemia in DiGeorge Disease
The mechanism of hypocalcemia in DiGeorge disease is primarily attributed to the underdevelopment or absence of the parathyroid glands, which are responsible for producing parathyroid hormone (PTH) [ 2 ]. PTH plays a crucial role in regulating calcium levels in the blood by stimulating the release of calcium from bones, increasing calcium absorption in the gut, and reducing calcium excretion in the urine.
Embryological Basis
The embryological basis of DiGeorge disease involves the abnormal development of the pharyngeal arch system, which gives rise to the parathyroid glands, thymus, and parts of the heart and great vessels [ 2 ]. This abnormal development leads to a range of clinical features, including hypocalcemia, congenital heart disease, and immunodeficiency.
Key Features
Some key features of hypocalcemia in DiGeorge disease include:
- Low levels of PTH, leading to decreased calcium absorption and increased calcium excretion [ 3 ]
- Underdevelopment or absence of the parathyroid glands [ 4 ]
- Association with congenital heart disease and other developmental abnormalities [ 2 ]
- Potential for thyroid C cell deficiency, which may contribute to the development of hypocalcemia [ 5 ]
Clinical Presentation
Hypocalcemia in DiGeorge disease can present in various ways, including: