Michael P. Whyte, M.D.

DEPARTMENT OF Internal Medicine
Keywords: bone disease, skeletal dysplasias, metabolism, alkaline phosphatase

Numerous metabolic bone diseases and skeletal dysplasias affect pediatric as well as adult patients. Many are heritable. For those that are genetically transmitted, an increasing number are understood at the molecular level. Medical treatment is available for most of the metabolic conditions, but for few of the dysplasias. At the Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, efforts are directed to diagnose, treat and investigate these conditions. Among the principal disorders encountered are X-linked hypophosphatemic (vitamin D-resistant) rickets, osteogenesis imperfecta (brittle bone disease), hypophosphatasia and disorders that cause focal or generalized osteosclerosis or osteopenia. However, the entire spectrum of pediatric metabolic bone diseases as well as skeletal dysplasias that can be confused with metabolic disorders are represented. Among the many clinical studies underway are: a long-term evaluation of the bioactive metabolite of vitamin D (calcitriol) and phosphate supplementation for X-linked hypophosphatemic rickets; quantitation of endogenous phosphocompound accumulation to provide diagnostic markers and prognosticators for hypophosphatasia; and assessment of the impact of dietary changes on the pathogenesis of high urine calcium levels in osteogenesis imperfecta. New syndromes and disorders are encountered and thoroughly characterized with mineral balance studies, bone densitometric techniques and iliac crest histomorphometry.

The laboratory not only provides routine assays to assess and follow mineral homeostasis but acts as a repository of biological specimens for collaborative studies. Such investigations are underway to locate and characterize the disease genes that cause X-linked hypophosphatemia, juvenile Paget disease, idiopathic hypoparathyroidism, hypophosphatasia, familial benign hypercalcemia, familial osteoporosis and various skeletal dysplasias. Phenotype/genotype correlation is being studied for several disorders. Investigators work closely with fellows and other faculty members.

In our laboratory at Barnes-Jewish Hospital (South Campus), we are searching for the gene defects that cause spondyloepiphyseal dysplasia tarda and X-linked recessive hypoparathyroidism. Mutation analysis of the bone alkaline phosphatase gene is underway for hypophosphatasia.