The study, “Clinical and Genetic Findings in a Chinese Cohort of Patients With DiGeorge Syndrome-Related Hypoparathyroidism,” was published in the journal Endocrine Practice.
DiGeorge syndrome (DGS) is a genetic disorder caused by the deletion (loss) of a small portion of chromosome 22. One of the many signs and symptoms of DGS includes low levels of calcium in the blood, a condition known as hypocalcemia, which also occurs in patients with hypoparathyroidism.
Hypoparathyroidism is caused by low levels of the parathyroid hormone (PTH) in the body, which is responsible for controlling the levels of calcium in the blood.
As hypocalcemia is a common feature to both disorders, and because DGS is very rare and can manifest in different ways, patients with DGS may remain undiagnosed for a long time or be misdiagnosed as having hypoparathyroidism without a known cause (idiopathic hypoparathyroidism).
In an effort to characterize the clinical features of DGS that may help physicians distinguish the disease from idiopathic hypoparathyroidism, researchers in China compared the medical records of 26 DGS patients who started showing symptoms of hypoparathyroidism during childhood, to those of 114 individuals with idiopathic hypoparathyroidism.
Results revealed that compared to individuals with idiopathic hypoparathyroidism, those with DGS started having hypocalcemia at a younger age (in most cases during infancy), had higher levels of PTH in the blood, and required lower doses of vitamin D supplementation or calcitriol (the active form of vitamin D) to maintain the same levels of calcium in the blood.
Three of the 26 DGS patients were clinically diagnosed before having genetic tests. Apart from one patient with a novel missense mutation in the TBX1 gene, the remaining 25 all had deletions in the same gene. (A missense mutation is an alteration of a single nucleotide — the building blocks of DNA — that alters protein composition.)
The novel mutation (p.Y490C) led to the replacement of the amino acid (the building blocks of proteins) tyrosine for cysteine at position 490 of the protein sequence.
Further experiments confirmed that this alteration significantly reduced the activity of the protein encoded by the TBX1 gene. This protein is a transcription factor, meaning that it controls the activity of certain genes.
“In this Chinese group of patients with DGS-related HP [hypoparathyroidism], a relatively earlier onset age and less severity of HP were found compared to that of patients with IHP [idiopathic hypoparathyroidism],” the researchers wrote.
“To improve diagnostic rate, extra-parathyroid manifestations should be investigated more frequently, and genetic testing is recommended for such patients,” they stated.
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