Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood.

Abstract

OBJECTIVE:

To describe an elderly patient with low serum alkaline phosphatase (ALP) activity detected after a pathologic fracture and to characterize hypophosphatasia in adult patients.

METHODS:

We present a case report of a 64-year-old woman, who was referred after sustaining an atraumatic femoral fracture treated successfully with intramedullary nailing. Clinical, biochemical, radiologic, and molecular studies explore the differential diagnosis of her hypophosphatasemia, and the features, diagnosis, and management of the adult form of hypophosphatasia are reviewed.

RESULTS:

Physical examination of our patient was revealing only for short stature. Bone mineral density evaluated by dual-energy x-ray absorptiometry was unremarkable. Biochemical investigations showed normal calcium, elevated inorganic phosphate, and low ALP levels in serum. In light of the hypophosphatasemia and pathologic fracture, the serum pyridoxal 5'-phosphate concentration was measured and found to be considerably elevated, a substantiation of the diagnosis of hypophosphatasia. Analysis of the gene encoding the "tissue-nonspecific" isoenzyme of ALP (TNSALP) demonstrated a novel, heterozygous, missense mutation causing her disorder.

CONCLUSION:

Hypophosphatasia is a rare inborn error of metabolism due to a deactivating mutation (or mutations) of the gene encoding TNSALP, in turn leading to global deficiency of TNSALP activity and inadequate skeletal mineralization and fractures. Our patient illustrates the importance of low serum ALP activity in the assessment of patients with fractures. No established treatment exists for hypophosphatasia, but the correct diagnosis should help to avoid the use of traditional therapies for osteoporosis or osteomalacia, which would be ineffective or potentially harmful.

• Authors: Hasnain M Khandwala, Steven Mumm, Michael P Whyte
• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Endocr Pract) 2006 Nov-Dec Vol. 12 Issue 6 Pg. 676-81 ISSN: 1934-2403 [Electronic] United States
• PMID: 17229666 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (blood, genetics, metabolism)
• DNA Mutational Analysis
• Female
• Femoral Fractures (etiology)
• Fractures, Spontaneous (etiology)
• Humans
• Hypophosphatasia (diagnosis, genetics)
• Middle Aged
• Mutation, Missense