Metabolic assessment in pure struvite stones formers: is it necessary? / Avaliação metabólica em formadores de cálculo de estruvita pura: é necessário?

Abstract Background and objective: Magnesium ammonium phosphate stones (MAP), also known as struvite stones, are associated with urinary infection and impairment of renal unit. The aim of this study is to evaluate the urinary metabolic risk factors for recurrence of renal calculi in patients submitted to nephrectomy due to MAP stones. Methods: We retrospectively reviewed the charts of patients > 18 years old submitted to total nephrectomy due to pure MAP stones and pure calcium oxalate (CaOx) stones from July 2006 to July 2016. Urinary metabolic parameters were assessed through 24-hour urine exams ≥ 3 months after nephrectomy. Urinary metabolic parameters and new event related to lithiasis were compared. Results: Twenty-eight and 39 patients were included in MAP and CaOx group, respectively. Abnormalities in 24-hour urine samples were similar between groups. Hypercalciuria occurred in 7.1 and 10.3% of patients in MAP and CaOx group, respectively (p = 0.66), whereas hypocitraturia was present in 65.2 and 59.0% of patients with MAP and CaOx group, respectively (p = 0.41). No significant difference in new events was found between MAP and CaOx groups (17.9 vs. 23.1%, respectively; p = 0.60). Conclusion: A 24-hour urine evaluation should be offered to patients submitted to nephrectomy due to pure MAP stones in order to detect metabolic risk, improve treatment, and prevent stone recurrence.

Resumo Contexto e objetivo: Cálculos de fosfato de amônio e magnésio (FAM), também conhecidos como cálculos de estruvita, estão associados à infecção urinária e ao comprometimento da unidade renal. O objetivo deste estudo é avaliar os fatores de risco metabólico-urinários para recorrência de cálculos renais em pacientes submetidos à nefrectomia devido a cálculo de FAM. Métodos: Revisamos retrospectivamente os prontuários de pacientes > 18 anos submetidos à nefrectomia total devido a cálculos de FAM puro e cálculos de oxalato de cálcio puro (OxCa) de julho de 2006 a julho de 2016. Os parâmetros metabólicos urinários foram avaliados através de exames de urina de 24 horas ≥ 3 meses após a nefrectomia. Os parâmetros metabólicos urinários e um novo evento relacionado à litíase foram comparados. Resultados: Vinte e oito e 39 pacientes foram incluídos nos grupos FAM e OxCa, respectivamente. As anormalidades em amostras de urina de 24 horas foram similares entre os grupos. A hipercalciúria ocorreu em 7,1 e 10,3% dos pacientes nos grupos FAM e OxCa, respectivamente (p = 0,66), enquanto a hipocitratúria esteve presente em 65,2 e 59,0% dos pacientes nos grupos FAM e OxCa, respectivamente (p = 0,41). Nenhuma diferença significativa em novos eventos foi encontrada entre os grupos FAM e OxCa (17,9 vs. 23,1%, respectivamente; p = 0,60). Conclusão: Uma avaliação de urina de 24 horas deve ser oferecida aos pacientes submetidos à nefrectomia devido a cálculos de FAM puro, a fim de detectar risco metabólico, melhorar o tratamento e prevenir a recorrência de cálculos.

X-linked hypophosphatemic rickets: a new mutation / Raquitismo hipofosfatêmico ligado ao X: uma nova mutação

Abstract Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient's outcome. Genetic analysis can help to establish a genotype-phenotype correlation.

Resumo O raquitismo fosfopênico pode ser causado por mutações no gene PHEX (ligado ao X do homólogo da endopeptidase que regula o fosfato). Atualmente, mais de 500 mutações no gene PHEX causam raquitismo hipofosfatêmico. Os autores relatam um caso clínico de uma menina de 4 anos com histórico familiar sem relevância, que apresentou falha no crescimento e arqueamento das pernas. Os exames laboratoriais mostraram hipofosfatemia, fosfatase alcalina elevada, cálcio normal, PTH levemente elevado e níveis normais de 25(OH)D e 1,25(OH)D. O estudo radiológico mostrou deformidades ósseas no rádio e no fêmur. O diagnóstico clínico do raquitismo fosfopênico foi realizado e o estudo genético detectou uma provável variante patogênica heterozigótica do gene PHEX: c.767_768del (p.Thr256Serfs*7). Esta variante não foi descrita anteriormente na literatura ou nas bases de dados. O conhecimento sobre novas mutações pode melhorar o desfecho de pacientes. A análise genética pode ajudar a estabelecer uma correlação genótipo-fenótipo.

Analysis of PHEX gene variant and prenatal diagnosis for a Chinese pedigree affected with X-linked hypophosphatemia / 中华医学遗传学杂志

OBJECTIVE@#To detect pathological variant in a Chinese pedigree affected with X-linked hypophosphatemia (XLH).@*METHODS@#Whole-exome sequencing was carried out to screen genetic variants in the proband and her parents. Candidate variant of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) was verified by Sanger sequencing of all members of the pedigree and the 100 healthy controls. Prenatal diagnosis was carried out on chorionic villi sample derived from the fetus of the proband.@*RESULTS@#A c.1256G>A (p. Gly419Glu) variant was identified in the PHEX gene of the proband and all other patients from this pedigree. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. Prenatal diagnosis suggested that the fetus also carried the c.1256G>A (p. Gly419Glu) variant.@*CONCLUSION@#The c.1256G>A (p. Gly419Glu) variant of the PHEX gene probably underlay the pathogenesis of XLH in this family. Discovery of the novel variant has enriched the mutational spectrum of the PHEX gene.

Analysis of PHEX gene variant and prenatal diagnosis for a Chinese pedigree affected with X-linked hypophosphatemia / 中华医学遗传学杂志

OBJECTIVE@#To detect pathological variant in a Chinese pedigree affected with X-linked hypophosphatemia (XLH).@*METHODS@#Whole-exome sequencing was carried out to screen genetic variants in the proband and her parents. Candidate variant of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) was verified by Sanger sequencing of all members of the pedigree and the 100 healthy controls. Prenatal diagnosis was carried out on chorionic villi sample derived from the fetus of the proband.@*RESULTS@#A c.1256G>A (p. Gly419Glu) variant was identified in the PHEX gene of the proband and all other patients from this pedigree. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. Prenatal diagnosis suggested that the fetus also carried the c.1256G>A (p. Gly419Glu) variant.@*CONCLUSION@#The c.1256G>A (p. Gly419Glu) variant of the PHEX gene probably underlay the pathogenesis of XLH in this family. Discovery of the novel variant has enriched the mutational spectrum of the PHEX gene.

PHEX Gene Mutations and Genotype-Phenotype Analysis of Korean Patients with Hypophosphatemic Rickets

X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH.