Expansile skeletal hyperphosphatasia: A new familial metabolic bone disease

We describe a new familial metabolic bone disease characterized by expandin g hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia, The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost a ll hearing in early childhood and suffered premature shedding of teeth. Ske letal pains began just before puberty. Swelling and aching of most middle p halanges in the hands is an especially troublesome manifestation. The mothe r also had episodes of symptomatic hypercalcemia first documented in late c hildhood and subsequently during intercurrent illness and postpartum lactat ion. Radiographs show hyperostosis and/or osteosclerosis predominantly in t he skull and appendicular skeleton, Long bones also are expanded considerab ly, especially the middle phalanges in the fingers. The mother's skeletal a bnormalities are more severe. Biochemical parameters of bone turnover, incl uding serum alkaline phosphatase (ALP) activity, are elevated substantially . In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling, In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteo cytic osteolysis. Measles virus gene transcripts were not detected in perip heral blood monocytes, Karyotyping was normal, 46,XX. Hyperphosphatasia wit h bone disease previously has been reported as either a sporadic or autosom al recessive condition. Expansile skeletal hyperphosphatasia (ESH) is proba bly inherited as an autosomal dominant trait with a high degree of penetran ce.