Expansile skeletal hyperphosphatasia: A new familial metabolic bone disease

M. P. Whyte, B. G. Mills, W. R. Reinus, M. N. Podgornik, G. David Roodman, F. H. Gannon, M. C. Eddy, W. H. McAlister

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We describe a new familial metabolic bone disease characterized by expanding 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 all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the bands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during inter-current illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including 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 osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance.

Original languageEnglish (US)
Pages (from-to)2330-2344
Number of pages15
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume15
Issue number12
StatePublished - 2000
Externally publishedYes

Fingerprint

Metabolic Bone Diseases
Hypercalcemia
Bone and Bones
Finger Phalanges
Osteosclerosis
Hyperostosis
Tooth Loss
Karyotyping
Measles virus
Osteolysis
Penetrance
Bone Remodeling
Bone Diseases
Diphosphonates
Deafness
Puberty
Lactation
Skull
Skeleton
Postpartum Period

Keywords

  • Alkaline phosphatase
  • Deafness
  • Hypercalcemia
  • Paget's bone disease

ASJC Scopus subject areas

  • Surgery

Cite this

Expansile skeletal hyperphosphatasia : A new familial metabolic bone disease. / Whyte, M. P.; Mills, B. G.; Reinus, W. R.; Podgornik, M. N.; Roodman, G. David; Gannon, F. H.; Eddy, M. C.; McAlister, W. H.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 15, No. 12, 2000, p. 2330-2344.

Research output: Contribution to journalArticle

Whyte, M. P. ; Mills, B. G. ; Reinus, W. R. ; Podgornik, M. N. ; Roodman, G. David ; Gannon, F. H. ; Eddy, M. C. ; McAlister, W. H. / Expansile skeletal hyperphosphatasia : A new familial metabolic bone disease. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2000 ; Vol. 15, No. 12. pp. 2330-2344.
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