ESPE Abstracts

Introduction: Primary hypoparathyroidism is a rare cause of hypocalcemia, complicating various disorders. Clinical presentation ranges from asymptomatic patients to paresthesia, cramps, seizures, stridor, laryngospasm, cardiac arrhythmias, basal ganglia calcification, subcapsular cataracts, and dental enamel hypoplasia. This study aims to present the cases of two patients with rare causes of primary hypoparathyroidism and highlight the need for standardization of calcium stress doses upon infections.

Methods: Patient 1 is an 8-year-old boy of Somali origin, presenting to the emergency department just after immigration, on account of lack of calcitriol and calcium carbonate medication, which was initiated in Turkey after seizures and hypocalcemia with no further information being available. Personal history included generalized seizures from early childhood. Clinical examination revealed alopecia, skin candidiasis, dental and skin deformities, as well as cataract upon ophthalmological evaluation. Diagnostic work up revealed primary hypoparathyroidism (Ca: 7.2 mg/dL, PTH: 2.76 pg/mL, 25OHD: 27ng/mL) and positive autoantibodies (ZnT8, LKM, adrenal), indicating a diagnosis of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-APECED. Patient 2 is a 4-year-old boy from Iraq, who presented to the emergency department due to febrile seizures occurring daily and an upper respiratory tract infection. Patient 2 was hospitalized in Turkey 2 years ago due to epileptic seizures attributed to hypocalcemia, although further details were unavailable. Clinical examination revealed severe growth failure, dysmorphic features, (dolichocephaly, microcephaly, low-set ears, delayed tooth eruption). Further evaluation revealed primary hypoparathyroidism (Ca: 5.8 mg/dL, PTH: 2.40 pg/mL, 25OHD: 23ng/mL), significant nephrocalcinosis of unknown etiology, as well as reduced unilateral hearing. A SARS-CoV-2 infection in both patients led to a serious hypocalcemia, necessitating hospitalization and intravenous calcium treatment.

Results: In Patient 1 whole exome sequencing (WES) analysis revealed an homozygous pathological mutation on AIRE NM_000383.4:c.260del, p.(Leu87fs), confirming the diagnosis of APECED. In Patient 2 WES showed an homozygous mutation on TBCE gene (c.155-166del12), setting a diagnosis of Hypoparathyroidism-Retardation-Dysmorphism syndrome. An expectant management approach was adopted and a multidisciplinary therapeutic plan was initiated. In both patients, hypoparathyroidism was treated with alfacalcidol and calcium carbonate to manage hypocalcemia in context of infection, that were subsequently titrated.

Conclusions: The different diagnostic context but the common pathophysiologic pathway of both patients highlight the heterogeneity of primary hypoparathyroidism. These patients benefit from early diagnosis and require comprehensive follow-up. COVID-19 infection may cause acute symptomatology in these patients. Standardizing a stress dose of oral calcium treatment upon infections can potentially prevent metabolic dysregulation and minimize hospitalizations by in-time management of this complication.