RESUMO
CONTEXT: Persistent hypercalciuria, with the attendant risk of nephrocalcinosis and eventual renal failure, is common in hypoparathyroid patients, especially those with activating mutations of the calcium-sensing receptor (CASR) gene, being treated with oral calcium and calcitriol. Treatment with replacement PTH may be warranted, although this has yet to be evaluated in children. OBJECTIVES: The objectives of this study were to identify the cause of the disorder in a young hypocalcemic patient and to assess the efficacy of treatment of the patient with recombinant human PTH(1-34). SUBJECT: An infant presenting with hypocalcemia at 3 wk of age was studied. METHODS: CASR gene mutation analysis was performed on genomic DNA of the proband and family members. The patient was treated with twice-daily administration of recombinant human PTH(1-34) over a 17-month period. RESULTS: The proband was heterozygous for a de novo novel missense mutation (L727Q), on the border between transmembrane helix 4 and intracellular loop 2 of the CASR. When transiently expressed in a human embryonic kidney 293 cell line, the mutant receptor demonstrated a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve vs. that for the wild-type receptor [EC(50); mutant, 2.59 +/- 0.11 mm (mean +/- se) vs. wild-type, 3.78 +/- 0.12 mm, P < 0.001]. During treatment with PTH(1-34), the patient had no further serious hypocalcemic episodes, and his urinary calcium excretion declined remarkably. CONCLUSION: PTH should be evaluated further as a treatment of autosomal dominant hypocalcemia in young patients.
Assuntos
Hipocalcemia/tratamento farmacológico , Hipocalcemia/genética , Mutação de Sentido Incorreto/genética , Hormônio Paratireóideo/uso terapêutico , Receptores de Detecção de Cálcio/genética , Cálcio/urina , Linhagem Celular , Dimerização , Embrião de Mamíferos , Expressão Gênica , Heterozigoto , Humanos , Lactente , Rim , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Receptores de Detecção de Cálcio/química , Proteínas Recombinantes/uso terapêutico , TransfecçãoRESUMO
We present a female with both Prader-Willi syndrome and Turner's syndrome, a combination not previously reported. We review her clinical presentation and discuss her growth pattern, mental development, and puberty, in relation to her mosaic Turner and Prader-Willi syndromes.
Assuntos
Mosaicismo , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/genética , Síndrome de Turner/complicações , Síndrome de Turner/genética , Criança , Deleção Cromossômica , Cromossomos Humanos Par 15 , Feminino , Transtornos do Crescimento/complicações , Transtornos do Crescimento/genética , Humanos , CariotipagemRESUMO
OBJECTIVE: To report a case of an azoospermic man diagnosed with 21-hydroxylase deficiency congenital adrenal hyperplasia who successfully conceived with intrauterine insemination (IUI) after hormonal and clomiphene citrate (CC) treatment. DESIGN: Case report. SETTING: Outpatient practice and academic hospital. PATIENT(S): A 32-year-old azoospermic man who presented for evaluation of male factor infertility. INTERVENTION(S): Semen analysis, ultrasonography, endocrinologic assays, hormonal treatment, CC, and IUI. MAIN OUTCOME MEASURE(S): Semen analysis demonstrating increased sperm count and motility, ultrasonography demonstrating persistent nodules in bilateral testes, endocrinologic assays demonstrating elevated FSH and LH after CC treatment. RESULT(S): Successful intrauterine pregnancy after IUI using the patient's sperm. CONCLUSION(S): Clomiphene citrate treatment in addition to hormonal manipulation in azoospermic patients with congenital adrenal hyperplasia can be successful in improving sperm count and motility to allow for successful conception using IUI. The presumed adrenal rests in the testes may not involute after adrenal suppression.
