Limits...
Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome.

Gok F, Chefetz I, Indelman M, Kocaoglu M, Sprecher E - Acta Orthop (2009)

Bottom Line: Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient.The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones.The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Nephrology, Gulhane Military Medical School, Ankara, Turkey.

ABSTRACT

Background and purpose: Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents.

Methods: Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient.

Results: Radiological examination revealed periosteal reaction, diaphysitis, and cortical hyperostosis, suggesting osteomyelitis or a bone neoplasm. The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones. The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS.

Interpretation: Molecular analysis represents an invaluable tool in the differential diagnosis of persistent cortical hyperostosis.

Show MeSH

Related in: MedlinePlus

(a) Radiograph demonstrating a subtle periosteal reaction in the midshaft of the left tibia (arrowhead). (b) A coronal T1-weighted sequence showing loss of normal fatty marrow in the tibia. (c) A post-contrast fat-suppressed coronal T1-weighted image revealing contrast enhancement in the marrow and adjacent soft tissues. (d) Radiograph showing a periosteal reaction (arrowheads) and medullary sclerosis of the right tibia. (e) An axial T1-weighted image demonstrating reduced bone marrow signal of the right tibia with adjacent soft tissue intensity. (f) A post-contrast fat-suppressed axial T1-weighted image revealing contrast enhancement in the marrow and juxtacortical soft tissue enhancement in the right tibia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2823226&req=5

Figure 0001: (a) Radiograph demonstrating a subtle periosteal reaction in the midshaft of the left tibia (arrowhead). (b) A coronal T1-weighted sequence showing loss of normal fatty marrow in the tibia. (c) A post-contrast fat-suppressed coronal T1-weighted image revealing contrast enhancement in the marrow and adjacent soft tissues. (d) Radiograph showing a periosteal reaction (arrowheads) and medullary sclerosis of the right tibia. (e) An axial T1-weighted image demonstrating reduced bone marrow signal of the right tibia with adjacent soft tissue intensity. (f) A post-contrast fat-suppressed axial T1-weighted image revealing contrast enhancement in the marrow and juxtacortical soft tissue enhancement in the right tibia.

Mentions: An 8-year old girl born to first-degree healthy consanguineous parents was admitted with painful swelling of the left lower leg that had lasted 10 days. Plain radiography showed a diaphyseal periosteal reaction (Figure 1a). Complete blood count was normal. Because of the absence of fever, a tumor was considered. MRI showed reduced signal intensity in the medullary bone with similar changes in the periosteum and soft tissues on T1-weighted images (Figure 1b). On T2-weighted scans, corresponding areas were hyperintense. Post-intravenous contrast images revealed enhancement of bone and adjacent soft tissues (Figure 1c). Antibiotic therapy (cephazolin sodium, 500 mg twice a day intravenously for 2 weeks) was instituted for suspected osteomyelitis. Shortly thereafter, both symptoms and radiographic findings resolved. 7 months later, the girl was re-admitted with right lower leg pain and swelling. Plain films and MRI showed similar findings to those observed previously in the left leg. Mild hyperostosis of the tibia was also noted (Figure 1d–f). Routine blood tests were normal. With a presumptive diagnosis of malignancy or recurrent osteomyelitis, the patient underwent bone biopsy, which showed reactive periostitis and normal osteoblastic cells. No organisms were identified in the aspirate, and cultures were sterile. Additional blood tests revealed increased serum phosphate (9.2 mg/dL; age-adjusted normal values: 3.6–5.9 mg/dL), normal serum creatinine, calcium, parathyroid hormone, and vitamin D levels. Serum phosphate levels were persistently high during a 12-month follow-up period. FGF23 C-terminal serum levels were elevated, as previously shown in HHS and HFTC (Topaz et al. 2004). Taken together, clinical, radiological, metabolic, and histopathologic findings suggested a diagnosis of HHS.


Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome.

Gok F, Chefetz I, Indelman M, Kocaoglu M, Sprecher E - Acta Orthop (2009)

(a) Radiograph demonstrating a subtle periosteal reaction in the midshaft of the left tibia (arrowhead). (b) A coronal T1-weighted sequence showing loss of normal fatty marrow in the tibia. (c) A post-contrast fat-suppressed coronal T1-weighted image revealing contrast enhancement in the marrow and adjacent soft tissues. (d) Radiograph showing a periosteal reaction (arrowheads) and medullary sclerosis of the right tibia. (e) An axial T1-weighted image demonstrating reduced bone marrow signal of the right tibia with adjacent soft tissue intensity. (f) A post-contrast fat-suppressed axial T1-weighted image revealing contrast enhancement in the marrow and juxtacortical soft tissue enhancement in the right tibia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823226&req=5

Figure 0001: (a) Radiograph demonstrating a subtle periosteal reaction in the midshaft of the left tibia (arrowhead). (b) A coronal T1-weighted sequence showing loss of normal fatty marrow in the tibia. (c) A post-contrast fat-suppressed coronal T1-weighted image revealing contrast enhancement in the marrow and adjacent soft tissues. (d) Radiograph showing a periosteal reaction (arrowheads) and medullary sclerosis of the right tibia. (e) An axial T1-weighted image demonstrating reduced bone marrow signal of the right tibia with adjacent soft tissue intensity. (f) A post-contrast fat-suppressed axial T1-weighted image revealing contrast enhancement in the marrow and juxtacortical soft tissue enhancement in the right tibia.
Mentions: An 8-year old girl born to first-degree healthy consanguineous parents was admitted with painful swelling of the left lower leg that had lasted 10 days. Plain radiography showed a diaphyseal periosteal reaction (Figure 1a). Complete blood count was normal. Because of the absence of fever, a tumor was considered. MRI showed reduced signal intensity in the medullary bone with similar changes in the periosteum and soft tissues on T1-weighted images (Figure 1b). On T2-weighted scans, corresponding areas were hyperintense. Post-intravenous contrast images revealed enhancement of bone and adjacent soft tissues (Figure 1c). Antibiotic therapy (cephazolin sodium, 500 mg twice a day intravenously for 2 weeks) was instituted for suspected osteomyelitis. Shortly thereafter, both symptoms and radiographic findings resolved. 7 months later, the girl was re-admitted with right lower leg pain and swelling. Plain films and MRI showed similar findings to those observed previously in the left leg. Mild hyperostosis of the tibia was also noted (Figure 1d–f). Routine blood tests were normal. With a presumptive diagnosis of malignancy or recurrent osteomyelitis, the patient underwent bone biopsy, which showed reactive periostitis and normal osteoblastic cells. No organisms were identified in the aspirate, and cultures were sterile. Additional blood tests revealed increased serum phosphate (9.2 mg/dL; age-adjusted normal values: 3.6–5.9 mg/dL), normal serum creatinine, calcium, parathyroid hormone, and vitamin D levels. Serum phosphate levels were persistently high during a 12-month follow-up period. FGF23 C-terminal serum levels were elevated, as previously shown in HHS and HFTC (Topaz et al. 2004). Taken together, clinical, radiological, metabolic, and histopathologic findings suggested a diagnosis of HHS.

Bottom Line: Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient.The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones.The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Nephrology, Gulhane Military Medical School, Ankara, Turkey.

ABSTRACT

Background and purpose: Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents.

Methods: Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient.

Results: Radiological examination revealed periosteal reaction, diaphysitis, and cortical hyperostosis, suggesting osteomyelitis or a bone neoplasm. The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones. The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS.

Interpretation: Molecular analysis represents an invaluable tool in the differential diagnosis of persistent cortical hyperostosis.

Show MeSH
Related in: MedlinePlus