In this abstract we report a case of Albright's syndrome associated with hypophosphatemic rickets and hyperthyroidism in a six-year-old girl. She had suffered from repeated fractures of her long bones owing to multiple locations of radiolucent areas and generalized skeletal demineralization. The biopsy in the lucent area revealed histologic appearance of fibrous dysplasia.
Child ; Female ; Femoral Fractures/etiology ; Fibrous Dysplasia, Polyostotic/*complications ; Human ; Hyperthyroidism/*complications ; Phosphates/*blood ; Rickets/*complications

Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Rickets ; diagnosis ; etiology ; therapy ; Treatment Outcome ; Vitamin D Deficiency ; complications

Humans ; Infant ; Rickets ; diagnosis ; pathology ; Risk Factors ; Vitamin D Deficiency ; complications ; diagnosis ; pathology

Acidosis, Renal Tubular ; complications ; diagnosis ; Child ; Diagnostic Errors ; Female ; Humans ; Medullary Sponge Kidney ; complications ; diagnosis ; Rickets ; diagnosis

OBJECTIVETo study the clinicopathologic features of osteomalacia or rickets-associated mesenchymal tumors.

METHODSThe clinical and pathologic findings of 10 cases of osteomalacia or rickets-associated mesenchymal tumors were evaluated. Hematoxylin and eosin stain, immunohistochemistry and histochemistry were performed on the archival paraffin sections.

RESULTSAmongst the 10 patients studied, 6 were males and 4 were females. Their age at the time of operation ranged from 28 to 69 years ( mean = 45.6 years). A history of long-standing bone pain, arthralgia, limitation in movement, hypophosphatemia and hyperphosphaturia was present in all cases. The duration of symptoms ranged from 2 to 27 years (mean = 9.6 years). The tumor size ranged from 1 to 7 cm (mean size = 3.52 cm). Microscopically, the tumors were composed of various mesenchymal cells, including spindled fibroblast-like cells, adipocytes, chondroid cells and mucinous cells. The background was rich in blood vessels. In 8 of the 10 cases, there was also dystrophic calcification in an unusual flocculent or "grungy" pattern. Peripheral woven bone shell formation was noted in 2 cases and non-urate crystal deposition in 2 cases. Mitotic figures were rare in 9 cases. In 1 of the 10 cases however, mitotic figures and bizarre cells were commonly encountered. On immunohistochemical study, the tumor cells were all positive for vimentin. There was focal positivity for smooth muscle actin and CD34 in 5 and 3 cases respectively. The staining for desmin, S-100 and AE1/AE3 was negative. Ki-67 proliferation index was less than 4% in 8 cases and 30% in 1 case. Alcian blue-positive mucinous matrix and mucinous degeneration around vessels were noted in 8 cases.

CONCLUSIONSMost of the osteomalacia or rickets-associated tumors are either benign or low-grade malignant mesenchymal tumors. They can be mistaken as other neoplasms due to the morphologic heterogeneity present. Thorough understanding of the associated clinical features and laboratory investigation results is helpful in arriving at the correct diagnosis.

Actins ; metabolism ; Adult ; Aged ; Antigens, CD34 ; metabolism ; Bone Neoplasms ; complications ; metabolism ; pathology ; Female ; Femoral Neoplasms ; complications ; metabolism ; pathology ; Humans ; Male ; Mesenchymoma ; complications ; metabolism ; pathology ; Middle Aged ; Osteomalacia ; complications ; Rickets ; complications ; Soft Tissue Neoplasms ; complications ; metabolism ; pathology ; Vimentin ; metabolism

OBJECTIVETo investigate the clinical features and mutations of the FAH gene.

METHODClinical records of two cases were collected, and diagnosis was made according to the diagnostic criteria of the International Organization for Rare Disorders (NORD). Genomic DNA was extracted from peripheral blood leukocytes with QIAamp DNA Mini Kit. The DNA extracts were subjected to direct sequencing for 14 exons together with adjacent fragments of FAH gene using ABI Prism 3730 Genetic Analyzer (Applied Biosystems, Foster City, CA) after PCR based on genomic DNA. The mutation source was verified by analyzing parents' exons corresponding to patients' mutation exons. The homology between human FAH enzyme and that of other species was surveyed using software Clustal X(European Bioinformatics Institute, Hinxton, Saffron Walde, UK). Polyphen (Polymorphism Phenotyping), available online, were used to predict possible impact of an amino acid substitution on structure and function of FAH enzyme. Polyphen calculates position-specific independent counts (PISC) scores for two amino acid variants in polymorphic position. A PISC scores that differ by > 2 were regarded as indicating the probability of damaging variants.

RESULTPatient 1 was a 5 months and 21 days-old boy who suffered from persistent diarrhea, hepatomegaly, ascites; Alpha-fetoprotein > 1210 µg/L, levels of tyrosine in blood and succinylacetone in urine were 110.8 µmol/L and 83.7 µmol/L. His sister suffered from tyrosinemia type 1. Direct sequencing showed a G to A transition in CDS position 455 and 1027. He was compound heterozygous for the mutation c.455G > A/c.1027G > A, which predicts a change from tryptophan to a stop codon (TGG > TAG) at position 152 (W152X) and a change from glycine to arginine (GGG > AGG) at position 343 respectively. Patient 2 was a 6 year and 1 month-old girl with late-onset rickets who had signs of hepatosplenomegaly, rachitic rosary, windswept knees. Hypophosphatemia and alkaline phosphatase 1620 IU/L were detected. Alpha-fetoprotein 412.8 µg/L, levels of tyrosine in blood and succinylacetone in urine were 835.8 µmol/L and 27.48 µmol/L. Rickets did not improve after administration of calcium and vitamine D3. She is homozygous for the mutation c.1027G > A/c.1027G > A, which predicts G343R. The parents were mutation carriers. Analysis by Clustal X on the alignment of amino acids residual reservation among different species showed that the locative amino acid was highly conserved. Polyphen software predicted G343R was probably damaging (PISC score 3.235).

CONCLUSIONChildren with tyrosinemia type 1 can have manifestations of persistent diarrhea or late-onset rickets. Physical examination can reveal hepatosplenomegaly, laboratory tests indicate markedly elevated serum concentration of alpha-fetoprotein and alkaline phosphatase in plasma and succinylacetone in urine, other members in family may have tyrosinemias or parents are consanguineous. Mutations c.455G > A and c.1027G > A can be detected in FAH gene of Chinese children.

Amino Acid Sequence ; Base Sequence ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diarrhea ; etiology ; genetics ; Exons ; Female ; Heptanoates ; urine ; Humans ; Hydrolases ; genetics ; Infant ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Rickets ; etiology ; genetics ; Tyrosine ; blood ; Tyrosinemias ; complications ; diagnosis ; genetics ; pathology ; alpha-Fetoproteins ; analysis

OBJECTIVETo study the association between vitamin D receptor (VDR) gene Apa I polymorphism and vitamin D deficiency rickets in children of Shanxi Han ethnic group, and to explore the significance of individual hereditary factors in the development of rickets.

METHODSThis was a case control study. The grouping criteria were serum 25(OH)D(3) level, blood bone alkaline phosphatase and clinical symptom, respectively. The laboratory test methods were enzyme linked immunoassay and radioimmunoassay. PCR-RFLP technology was applied to examine VDR gene Apa I site polymorphism and Hardy-Weinberg hereditary balance test was used to examine the coincidence of gene distribution.

RESULTSFrequencies of AA, Aa and aa genotypes were 5.0%, 52.5% and 42.5% in the rickets group and 4.4%, 55.9% and 39.7% in the control group, respectively. Frequencies of A and a genotypes were 31.3% and 68.7% in the rickets group and 32.3% and 67.7% in the control group, respectively. There was not significant difference in the frequency distribution of VDR genotype and allelic genes between two groups (chi(2) = 0.089, P > 0.05; chi(2) = 0.028, P > 0.05). There was significant difference in the serum 25(OH)D(3) between two groups (t = -8.919, P < 0.01).

CONCLUSIONThe distribution of VDR gene Apa I polymorphism in children of Han ethnic group is balanced relatively. The Frequency of a allelic genes is 67.7% which is therefore the superior gene. VDR gene polymorphism might not be important in an individual's susceptibility to development of vitamin D deficiency.

Calcifediol ; blood ; Calcitriol ; deficiency ; Case-Control Studies ; Child, Preschool ; China ; ethnology ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Radioimmunoassay ; Receptors, Calcitriol ; genetics ; Rickets ; blood ; etiology ; genetics ; Vitamin D Deficiency ; complications ; genetics