Abstracts presented at the 27th Annual Congress of the Belgian Society of Internal Medicine, 1-2 December 2023, Dolce La Hulpe, La Hulpe, Belgium

Introduction: The term pseudohypoparathyroidism was introduced in 1942 by Albright et al. to describe several patients presenting hypocalcemia and hyperphosphatemia in association with short stature, short metacarpals and metatarsals, obesity as well as neurocognitive impairment (1). These findings are now referred as Albright’s hereditary osteodystrophy (AHO). Autoimmune polyendocrinopathy is characterized by autoimmune activity against more than one endocrine organ. We herein present a family (the mother and the daughter) affected with AHO and autoimmune polyendocrinopathy features. We show some preliminary genetic studies. Case reports: The index case is a 69 years old woman (patient A) , measuring 1m 47 and weighting 58 kg. She was diagnosed with Hashimoto Thyroiditis in 1982 and Biermer disease in 1982 (autoimmune polyendocrinopathy type 3, see table 1). Because of muscle cramps, biological investigation revealed in 2010: serum calcium: 2.10 mmol/L (2.15-2.6), phosphates: 1.08 mmol/L (0.74-1.51), PTH: 187 pg/ml, 25 vitD: 35 ng/ml (>20 ), IGF1: 114 ng/ml (32-226), GH: 0.7 ng/ml. In 2018, AHO was suspected on the basis of hypocalcemia, short stature and bilateral short 4th and 5th metacarpals and phalanges. Osteodensitometry was normal. GNAS gene sequencing identified a novel heterozygous variant c.970 56GT>T (class III). In silico analysis predict splicing defects.
Her daughter (Patient B) is 47 years old, measures 1m45 and weights 41 kg. She was diagnosed with Hashimoto Thyroiditis in 1989. Biological investigations revealed: serum calcium: 2.10 mmol/L (2.15-2.6), phosphates: 1.2 mmol/L (0.74-1.51), PTH: 131 pg/ml, 25 vitD: 24 ng/ml (>20 ). She presented Raynaud’s phenomenon and cryoglobulinemia in 2022. Because of short stature, brain calcifications, and bilateral short 4th and 5th metacarpals, autosomal dominant AHO is also suspected. Genetic analysis is ongoing. Conclusion: AHO is caused by mutations and/or epigenetic changes at the complex of GNAS locus on chromosome 20q13.3. It is an underdiagnosed cause of paresthesias and Fahr’s disease. Heterozygous maternal GNAS mutations cause variable degrees of PTH resistant hypocalcemia. Reduced Gsa activity may result in loss of endocrine function, and can develop resistance to other hormones including TSH, GH, gonadotropins, and calcitonin. The combination of AHO and autoimmune polyendocrinopathies is very rare