Osteosclerosis in two brothers with autosomal dominant pseudohypoparathyroidism type 1b: bone histomorphometric analysis.
OBJECTIVE
Pseudohypoparathyroidism (PHP) is a heterogeneous disorder characterized by hypocalcemia and hyperphosphatemia resulting from selective renal resistance to parathyroid hormone (PTH). One autosomal dominant form of PHP type 1b (PHP-Ib) is most frequently caused by a maternally inherited 3-kb deletion within STX16, the gene encoding syntaxin 16. To date, increased bone mineral density (BMD) has been described only in PHP type 1a, and there is a lack of detailed information on bone histomorphometry in PHP-Ib. The objective of this report was to present trans-iliac static and dynamic histomorphometry in two brothers with the 3-kb deletion in the STX16 region and elevated BMD.


METHODS
Observational study of two brothers (age 18.0 and 22.7 years) with the 3-kb STX16 deletion and increased BMD.


RESULTS
The brothers had elevated PTH (146 pg/ml (15.6 pmol/l) and 102 pg/ml (10.9 pmol/l); normal: 10-64 pg/ml (1.1-6.8 pmol/l)) and striking osteosclerosis (lumbar spine areal BMD Z-scores: +5.4 and +4.9). Bone histomorphometry showed marked elevations in cortical width for both brothers (241 and 209% of the mean result expected for age), with elevations in the bone formation rate on the endocortical (119 and 260% of the healthy mean) and trabecular (220 and 190% of mean) surfaces.


CONCLUSIONS
Our findings suggest that PTH in this PHP-Ib genotype can increase cortical thickness due to its anabolic effect on endocortical bone, and underscore the heterogeneity in the skeletal phenotype among patients with PHP-Ib.
Pediatric Bone Health Clinical and Research Programs, Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada.
Anne Marie
AM
Sbrocchi
Frank
F
Rauch
Margaret L
ML
Lawson
Stasia
S
Hadjiyannakis
Sarah
S
Lawrence
Murat
M
Bastepe
Harald
H
Jüppner
Leanne Marie
LM
Ward
D000293:Adolescent; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000473:pathology*; D006801:Humans; D008297:Male; D010026:Osteosclerosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D011547:Pseudohypoparathyroidism / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult