Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. J Bone Miner Res 2009 Aug;24(8):1493-505
Date
04/02/2009Pubmed ID
19335222DOI
10.1359/jbmr.090308Scopus ID
2-s2.0-68949100637 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Hypophosphatasia (HPP) is the inborn error of metabolism characterized by low serum alkaline phosphatase (ALP) activity caused by inactivating mutations within TNSALP, the gene that encodes the "tissue-nonspecific" isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate, a TNSALP substrate, inhibits hydroxyapatite crystal growth leading to rickets or osteomalacia. Chronic recurrent multifocal osteomyelitis (CRMO) is the pediatric syndrome of periarticular pain and radiographic changes resembling infectious osteomyelitis but without lesional pathogens. Some consider CRMO to be an autoinflammatory disease. An unrelated boy and girl with the childhood form of HPP suffered chronic, multifocal, periarticular pain, and soft tissue swelling. To investigate this unusual complication, we evaluated their cumulative clinical, biochemical, radiological, and histopathological findings and performed mutation analysis of their TNSALP alleles. The earliest radiographic disturbances were typical of childhood HPP. Subsequently, changes consistent with CRMO developed at sites where there was pain, including lucencies, osteosclerosis, and marked expansion of the underlying metaphyses. Bone marrow edema was shown by MRI. Biopsies of affected bone showed nonspecific histopathological findings and no pathogens. The boy was heterozygous (c.1133A>T, p.D378V) and the girl compound heterozygous (c.350A>G, p.Y117C, c.400_401AC>CA, p.T134H) for different TNSALP missense mutations. Nonsteroidal anti-inflammatory drugs diminished their pain, which improved or resolved at maturity. HPP should be considered when CRMO is a diagnostic possibility. Metaphyseal radiographic changes and marrow edema associated with periarticular bone pain and soft tissue swelling suggestive of osteomyelitis can complicate childhood HPP.
Author List
Whyte MP, Wenkert D, McAlister WH, Mughal MZ, Freemont AJ, Whitehouse R, Baildam EM, Coburn SP, Ryan LM, Mumm SMESH terms used to index this publication - Major topics in bold
AdolescentAlkaline Phosphatase
Chronic Disease
Diagnosis, Differential
Female
Humans
Hypophosphatasia
Male
Mutation, Missense
Osteomyelitis
Recurrence