Two cases of late-diagnosed non-surgical hypoparathyroidism

Abstract

Abstract. Hypoparathyroidism is characterized by low parathyroid hormone levels, low calcium levels, and high phosphate levels in the blood. The most common cause is neck surgery. Non-surgical hypoparathyroidism (Ns-HypoPT) can have various causes, including genetic ones. The most common genetic cause of Ns-HypoPT is the loss of the q11 region (22q11) on chromosome 22, which results in hypoplasia of the parathyroid glands. 22q11 syndrome is also known as DiGeorge syndrome (DGS). The acronym «CATCH  22» refers to the five clinical manifestations of DGS: Cardiac defects; Abnormal facies – facial dysmorphia; Thymic hypoplasia; Cleft palate; Hypocalciemia (HC). Diagnosis of DGS can be complicated due to the phenotype variation. DGS is suspected in the presence of at least one CATCH22 sign, molecular genetic methods confirm or refute the diagnosis. The publication presents two cases of Ns-HypoPT in adults who were not diagnosed in a timely manner. In both cases, HC with a decrease in PTH levels without a surgical history indicates Ns-HypoPT. Using nucleotide sequence analysis and
deletion/duplication testing of a panel of 2,211 genes in case №1, pathogenic variants were identified in three genes: TBX1 (associated with autosomal dominant DGS); LZTR1 (associated with autosomal dominant schwannomatosis and autosomal dominant and autosomal recessive Noonan syndrome); CLCN1 (associated with autosomal dominant and recessive congenital myotonia). Case 1 is characterized by the combination of DGS and Graves’ disease. Despite the different etiology of Ns-HypoPT (in case 1 it is a component of DGS, and in case 2 the etiology has not yet been established), in both cases HC was detected late and was treated ineffectively for a long time. The use of calcitriol [1,25 (OH)2 D3], the active form of vitamin D3, at a dosage of 1.25 μg/day (case 1) and 1.75 μg/day (case 2) increased calcium levels and reduced HC  ymptoms.