TY - JOUR
T1 - Neonatal lethal osteochondrodysplasia with low serum levels of alkaline phosphatase and osteocalcin
AU - Wyckoff, Myra H.
AU - El-Turk, Chirine
AU - Laptook, Abbot
AU - Timmons, Charles
AU - Gannon, Francis H.
AU - Zhang, Xiafang
AU - Mumm, Steven
AU - Whyte, Michael P.
PY - 2005/2
Y1 - 2005/2
N2 - Neonatal lethal skeletal dysplasias are rare and typically involve thoracic malformations and severe limb shortening. We report on a newborn boy manifesting an osteochondrodysplasia associated with fatal respiratory insufficiency who had normal lung volumes and extremity lengths. His disorder featured aberrant skeletal patterning and defective ossification including a severely osteopenic skull, apparent absence of clavicles, and clefting of the mandible and vertebrae. Serum alkaline phosphatase and osteocalcin levels were markedly low. Biochemical studies suggested parathyroid insufficiency probably from critical illness. Histopathology at autopsy excluded impaired mineralization of skeletal matrix, but endochondral bone formation appeared disorganized with growth plate clustering of chondrocytes in hypertrophic zones and in zones of provisional calcification. Parathyroid glands were not found. Despite features of two distinctive heritable entities, hypophosphatasia and cleidocranial dysplasia, the cumulative findings did not match either condition, and no mutations were found in either the tissue nonspecific ALP isoenzyme or core-binding factor genes, respectively, or in the genes encoding osteocalcin or the osteoblast transcription factor osterix. This patient could represent the extreme of cleidocranial dysplasia (a disorder not always associated with structural mutation in core-binding factor A1), but more likely he defines a unique osteochondrodysplasia disrupting both intramembranous and endochondral bone formation.
AB - Neonatal lethal skeletal dysplasias are rare and typically involve thoracic malformations and severe limb shortening. We report on a newborn boy manifesting an osteochondrodysplasia associated with fatal respiratory insufficiency who had normal lung volumes and extremity lengths. His disorder featured aberrant skeletal patterning and defective ossification including a severely osteopenic skull, apparent absence of clavicles, and clefting of the mandible and vertebrae. Serum alkaline phosphatase and osteocalcin levels were markedly low. Biochemical studies suggested parathyroid insufficiency probably from critical illness. Histopathology at autopsy excluded impaired mineralization of skeletal matrix, but endochondral bone formation appeared disorganized with growth plate clustering of chondrocytes in hypertrophic zones and in zones of provisional calcification. Parathyroid glands were not found. Despite features of two distinctive heritable entities, hypophosphatasia and cleidocranial dysplasia, the cumulative findings did not match either condition, and no mutations were found in either the tissue nonspecific ALP isoenzyme or core-binding factor genes, respectively, or in the genes encoding osteocalcin or the osteoblast transcription factor osterix. This patient could represent the extreme of cleidocranial dysplasia (a disorder not always associated with structural mutation in core-binding factor A1), but more likely he defines a unique osteochondrodysplasia disrupting both intramembranous and endochondral bone formation.
UR - http://www.scopus.com/inward/record.url?scp=14044268243&partnerID=8YFLogxK
U2 - 10.1210/jc.2004-0251
DO - 10.1210/jc.2004-0251
M3 - Article
C2 - 15562030
AN - SCOPUS:14044268243
SN - 0021-972X
VL - 90
SP - 1233
EP - 1240
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -