ESPE Abstracts (2023) 97 P1-412

ESPE2023 Poster Category 1 Bone, Growth Plate and Mineral Metabolism (46 abstracts)

Juvenile Paget's Disease: Evaluation of Novel Mutation and Treatment Response

Sare Betul Kaygusuz 1 , Mustafa Gokoglu 2 & Serap Turan 3

1Kahramanmaras City Hospital, Department of Pediatric Endocrinology, Kahramanmaras, Turkey. 2Kahramanmaras City Hospital, Department of Medical Genetics, Kahramanmaras, Turkey. 3Marmara University School of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey

Introduction: Juvenile Paget's Disease(JPD) is an extremely rare disease of bone characterized by progressive painful bone deformities, fractures and increased bone turnover. Findings also include deafness, loss of vision, vascular calcification and aneurysm. Here, we report two siblings presented with recurrent fractures and diagnosed as JPD by very high alkaline phosphatase levels and radiographic findings. A novel homozygous mutation in the TNFRSF11B gene was detected in both siblings.

Case: A 148/12-year-old male (case 1) presented with recurrent fractures. He was a product of consanguineous marriage of healthy parents. On initial examination, height SDS was −7,09(117cm), weight SDS −4,27(29 kg) and head circumference SDS +6.9(69 cm). He was noted to have severely deformed extremities, pectus carinatum, pseudoxanthoma elasticum, and macrocephaly. Laboratory tests showed very high levels of alkaline phosphatase(ALP)(10000 IU/L). X-rays showed increased diploic distance, enlargement-osteopenia and trabeculation of long bones. JPD was considered because of the family history of consanguineous marriage, history of recurrent fractures, radiological findings, and high ALP levels. His 11-month-old sister(case 2), who had a history of recurrent fractures, had a height of 73 cm(-0.49 SDS), weight of 8 kg(-1.18 SDS) and head circumference of 45.5 cm(-0.07 SDS). She noted to have deformed extremities. Laboratory tests showed high levels of ALP(3718 IU/L). A novel homozygous mutation in the TNFRSF11B gene was detected in both siblings. Clinical improvement and near normalization of ALP values was observed with intravenous pamidronate therapy. During the treatment period, no fracture was observed in both patients, a significant reduction in existing pain was observed in case 1, and the gain of gross motor skills was observed in case 2.

Discussion: It is predicted that the homozygous mutation in the TNFRSF11B gene that causes JPD, which we described in our cases, affects 'splicing' in intron 1 and leads to a truncated protein in which the entire ligand-binding region is lost. In both cases, severe JPD, in which the symptoms started in the first year, was observed, and a significant decrease in ALP values and improvement in clinical symptoms were observed after treatment. Improvement in bone symptoms after bisphosphonate treatment has been reported in the literature, but data on the improvement of non-skeletal findings and long-term follow-up are limited. Two cases are presented to evaluate the diagnosis, follow-up and treatment of the disease.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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