Endocrine Abstracts (2017) 49 S1.1 | DOI: 10.1530/endoabs.49.S1.1

Congenital hypoparathyroidism

Agnes Linglart


France.


The most common causes of hypoparathyroidism in children are the lack of or the impaired development of the parathyroid glands due to genetic/chromosomal alterations and the abnormal signaling of the Ca(2+)-sensing receptor (CaSR). The latter refers to autosomal dominant hypocalcemia (ADH) mainly caused by heterozygous activating mutations in CASR encoding CaSR (ADH type 1), and exceptionally caused by activating mutations of GNA11 encoding the Gq/11 protein (ADH type 2). Hypoparathyroidism can also be caused by an autoimmune process, mainly in the context of AIRE mutations. However, in many children, the origin of the hypoparathyroidism remains undiscovered. In a recent national French survey gathering 142 children affected with hypoparathyroidism performed by MAC, 43% of the patients were diagnosed before the age of 1 year. The main causes of the PTH insufficiency were 22q1.1 deletion (31%), ADH1 (13%), AIRE mutations (10%) and cervical surgery (7%). The etiology is still unknown in 23% of the children. Due to the high calcium needs of the skeleton during infancy and childhood, hypoparathyroidism in children is often symptomatic and is diagnosed because of the clinical symptoms of hypocalcemia (muscle spasms, laryngospasm, seizures). Children may present with unspecific features such as cognitive and or motor delay, slowness, ungueal, dental and skin anomalies. In addition, clinical characteristics due to the disease itself causing the hypoparathyroidism may be present such as candidosis, conotruncal cardiac defect, renal and/or uterine malformation. Once hypoparathyroidism has been diagnosed in a child, a comprehensive work-up should be performed to identify the disease-causing defect. The investigations depends on the age of the child (neonate, child, adolescent), and on the clinical features associated with the hypocalcemia. The diagnosis is of importance for the management of follow-up and treatment. The management of hypoparathyroidism in children relies upon calcium supplements and vitamin D analogs. Following the initial period of profound hypocalcemia which may require IV infusion of calcium and high doses of vitamin D analogs (up to 4 μg/day of alfacalcidol), the conventional therapy should aim at absence of clinical symptoms, low-normal level of serum calcium (2–2.2 mmol/l), avoiding hyperphosphatemia and having normal urinary calcium excretion. In some children, this may be a challenging management requiring the use of thiazide diuretics, phosphate binders, calcium supplements and in refractory cases, recombinant PTH. It has become obvious in the past ten years that we need to i- obtain more data on the long-term evolution of children affected with hypoparathyroidism, ii- adjust our decision rules for the identification of the cause of hypoparathyroidism in the context of next generation sequencing and gene panels or whole exome sequencing, and iii- develop guidelines for the management of hypoparathyroidism in children including the specificity of ADH.

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