Abstract：
Familial hypocalciuric hypercalcemia (FHH) is one of the conditions that should be considered in the differential diagnosis of hypercalcemia and normo-hypophosphatemia in childhood. Heterozygous Calcium-sensing receptor (CASR) gene mutations cause FHH, and homozygous CASR gene mutations cause neonatal severe primary hyperparathyroidism (NSHPT). Cinacalcet is an allosteric modulator of Calciumsensing receptor (CaSR), and has been used in the treatment of these clinical entities in recent years.
A 26-month-old boy was examined for a recurrent rash. During the evaluation, hypercalcemia (13.3 mg/ dL), hypophosphatemia (2.3 mg/dL) and inappropriately normal PTH level (67 pg/mL) were observed. Neck and renal ultrasonography were normal. The parathyroid scintigraphy was unremarkable. The patient`s family members were also evaluated, and hypocalciuria (fractional excretion of calcium were 0.01%, 0.04% on two separate tests) was detected concurrently with the patient`s hypercalcemia. The mother`s serum calcium was 10.2 mg/dL, the father`s was 10.6 mg/dL, and the brother`s was 12.8 mg/dL. CASR gene sequencing showed a novel homozygous mutation in exon 4 (c.1057G > A), which had generated a substitution of the amino acid glutamate to lysine at codon 353 (p.Glu353Lys). This mutation was homozygous in the children and heterozygous in the parents. Fluid hydration, furosemide, oral phosphorus, prednisolone, pamidronate and cinacalcet treatments were used in the management of hypercalcemia of the proband. A longer and more effective control was achieved with cinacalcet treatment.
FHH can be seen in heterozygous as well as homozygous CASR gene mutations. Different clinical findings may occur in different individuals from the same family. Cinacalcet therapy can be used successfully in the treatment of individuals with FHH.
A 26-month-old boy was examined for a recurrent rash. During the evaluation, hypercalcemia (13.3 mg/ dL), hypophosphatemia (2.3 mg/dL) and inappropriately normal PTH level (67 pg/mL) were observed. Neck and renal ultrasonography were normal. The parathyroid scintigraphy was unremarkable. The patient`s family members were also evaluated, and hypocalciuria (fractional excretion of calcium were 0.01%, 0.04% on two separate tests) was detected concurrently with the patient`s hypercalcemia. The mother`s serum calcium was 10.2 mg/dL, the father`s was 10.6 mg/dL, and the brother`s was 12.8 mg/dL. CASR gene sequencing showed a novel homozygous mutation in exon 4 (c.1057G > A), which had generated a substitution of the amino acid glutamate to lysine at codon 353 (p.Glu353Lys). This mutation was homozygous in the children and heterozygous in the parents. Fluid hydration, furosemide, oral phosphorus, prednisolone, pamidronate and cinacalcet treatments were used in the management of hypercalcemia of the proband. A longer and more effective control was achieved with cinacalcet treatment.
FHH can be seen in heterozygous as well as homozygous CASR gene mutations. Different clinical findings may occur in different individuals from the same family. Cinacalcet therapy can be used successfully in the treatment of individuals with FHH.
摘要：
背景：家族性低钙血症高钙血症（FHH）是儿童高钙血症和正常低磷血症的鉴别诊断中应考虑的疾病之一。杂合钙敏感受体(CASR)基因突变导致FHH,纯合子CASR基因突变导致新生儿重度原发性甲状旁腺功能亢进(NSHPT)。Cinacalcet是钙敏感受体（CaSR）的变构调节剂，近年来已用于治疗这些临床实体。
方法：对一名26个月大的男孩进行了皮疹复发检查。在评估过程中,高钙血症（13.3mg/dL），观察到低磷血症（2.3mg/dL）和不适当的正常PTH水平（67pg/mL）。颈部和肾脏超声检查正常。甲状旁腺显像无明显变化。还对患者的家属进行了评估，和低钙尿（钙的排泄分数为0.01％，在两个单独的测试中检测到0.04％）与患者的高钙血症同时进行。母亲的血清钙为10.2mg/dL，父亲的是10.6毫克/分升，和兄弟的是12.8毫克/分升。CASR基因测序显示外显子4出现新的纯合突变(c.107G>A),它在密码子353处产生了氨基酸谷氨酸到赖氨酸的取代（p。Glu353Lys）。这种突变在儿童中是纯合的，在父母中是杂合的。流体水合,呋塞米,口服磷，泼尼松龙,帕米膦酸盐和西那卡塞治疗用于先证者高钙血症的治疗。西那卡塞治疗可实现更长，更有效的控制。
结论：FHH可以在杂合和纯合CASR基因突变中看到。不同的临床表现可能发生在同一家庭的不同个体中。Cinacalcet疗法可成功用于治疗FHH患者。
方法：对一名26个月大的男孩进行了皮疹复发检查。在评估过程中,高钙血症（13.3mg/dL），观察到低磷血症（2.3mg/dL）和不适当的正常PTH水平（67pg/mL）。颈部和肾脏超声检查正常。甲状旁腺显像无明显变化。还对患者的家属进行了评估，和低钙尿（钙的排泄分数为0.01％，在两个单独的测试中检测到0.04％）与患者的高钙血症同时进行。母亲的血清钙为10.2mg/dL，父亲的是10.6毫克/分升，和兄弟的是12.8毫克/分升。CASR基因测序显示外显子4出现新的纯合突变(c.107G>A),它在密码子353处产生了氨基酸谷氨酸到赖氨酸的取代（p。Glu353Lys）。这种突变在儿童中是纯合的，在父母中是杂合的。流体水合,呋塞米,口服磷，泼尼松龙,帕米膦酸盐和西那卡塞治疗用于先证者高钙血症的治疗。西那卡塞治疗可实现更长，更有效的控制。
结论：FHH可以在杂合和纯合CASR基因突变中看到。不同的临床表现可能发生在同一家庭的不同个体中。Cinacalcet疗法可成功用于治疗FHH患者。
