Hypercalcaemia in infancy; a presenting feature of spinal muscular atrophy.

A 10 month old girl presented with a history of constipation from early life. She was found to be hypercalcaemic with hypercalciuria and nephrocalcinosis. Her mild motor delay and hypotonia were thought to be linked to chronic hypercalcaemia, but when these features failed to improve despite normocalcaemia on a low calcium diet the possibility of neuromuscular disease was explored in more detail. She was subsequently found to have spinal muscular atrophy type 2. We suspect that the hypercalcaemia with hypercalciuria observed in this case reflects altered bone turnover secondary to reduced muscular activity.     

儿童非霍奇金淋巴瘤合并高钙血症1例并文献复习

目的探讨儿童恶性肿瘤相关性高钙血症临床特征,提高对本病的认识及抢救成功率。方法结合1例高钙血症患儿的临床及实验室资料并进行相关文献复习。结果 1例9岁女孩,因原发于腹部的非霍奇金淋巴瘤(成熟B细胞表型)入院,入院后嗜睡、少尿,查血钙5.36 mmol/L,迅速出现肾功能衰竭,经补液、利尿及血液透析等治疗后血钙下降。结论儿童非霍奇金淋巴瘤合并高钙血症罕见,儿科血液专业医师应充分认识本病的危险性及其治疗原则。     

Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation.

A 3 year old girl presented with malignant osteopetrosis, which was treated by allogeneic bone marrow transplantation. Successful engraftment was complicated by prolonged hypercalcaemia, which was controlled by a combination of a bisphosphonate, phosphate infusions, vigorous resalination, and salmon calcitonin. She was alive and well 16 months after the transplant.     

Bones, groans and blasts

A 14-year-old girl presented with the acute onset of gastrointestinal symptoms due to hypercalcaemia. Chest X-ray revealed osteolytic lesions in the ribs which in conjunction with a normal parathyroid hormone level raised the possibility of malignancy. Despite the absence of blast cells in her blood film, the bone marrow biopsy was diagnostic of acute lymphoblastic leukaemia. She responded well to treatment with pamidronate and chemotherapy.     

Age at diagnosis and abilities in idiopathic hypercalcaemia.

Forty three children aged 6 to 16 years with a documented history of idiopathic infantile hypercalcaemia were assessed on a variety of cognitive and behavioural measures. No relation was found between the age at which hypercalcaemia was diagnosed and subsequent full scale intelligence quotients (IQ) and reading or spelling abilities. Verbal IQ was, however, significantly higher than performance IQ, which had an inverse relation with age at diagnosis. Furthermore, scores for deviant behaviour were found to correlate with age at diagnosis. Thus the characteristic psychological profile of this syndrome may be in part a function of hypercalcaemia during infancy.     

Primary hyperparathyroidism in a 14 year old girl presenting with bone deformities

A 14 year old girl with bilateral genu valgum of 6 years duration was brought for evaluation of primary hyperparathyroidism. She had clinical features of rickets such as frontal bossing, rachitic rosary, lumbar lordosis and fixed adduction deformity of the left leg. She had undergone osteotomy earlier for correction of these deformities without benefit. Laboratory investigations showed hypercalcaemia and hypophosphataemia, with elevated alkaline phosphatase and parathyroid hormone levels. A skeletal survey showed generalized decreased density of bone and brown tumours and, coincidentally, a right renal calculus. A computerized tomography scan of the neck and thallium-technetium subtraction scan delineated an adenoma of the left superior parathyroid gland, which was surgically removed. Parathyroid adenoma manifesting with bone deformities, especially genu valgum, is very rare in children. Early diagnosis and prompt treatment is essential to prevent such deformities.     

Failure of calcitriol treatment in a patient with malignant osteopetrosis

In an attempt to stimulate bone resportion, a 10-week-old infant with malignant infantile osteopetrosis was treated with high doses of calcitriol, a potent bone resorption stimulatory agent, combined with a low calcium diet to prevent hypercalcaemia. Although calcitriol administration was initiated at this very young age, our patient did not show any clinical, radiological, or histological improvement. Despite reports of positive results of this treatment in the literature, our patient did not reveal any signs of bone resorption. She eventually died from the complications of osteopetrosis at the age of 6 months after 88 days of therapy.     

Rhabdoid Wilms' tumour and prostaglandin-mediated hypercalcaemia

A nine-month-old girl with a rare rhabdoid variant of Wilms' tumour but no sign of bony metastases developed hypercalcaemia both at the time of diagnosis and at relapse. Tissue culture studies showed that primary tumour tissue and cells cultured from it released significant bone resorting activity, attributable to prostaglandins, into the culture medium, whereas tissue from a normal kidney and a Wilms' tumour not associated with hypercalcaemia did not. Serum parathyroid hormone (PTH) levels were normal and PTH was not found in the culture medium of tumour tissue. These results are consistent with the hypothesis that tumour-derived prostaglandins were responsible for the hypercalcaemia in this patient.     

Long-term control of hypercalcaemia in an infant with williams-Beuren syndrome after a single infusion of biphosphonate (Pamidronate)

AIM: To report the efficacy of Pamidronate to treat hypercalcaemia in a patient with Williams-Beuren syndrome (WBS). RESULTS: We report a 14-mo-old male infant presenting hypercalcaemia, elfin face and other dysmorphological features of WBS, confirmed by the FISH fluorescent test. Due to the marked symptomatic hypercalcaemia, 13.0 mg/dl intravenous Pamidronate was administered in a single dose of 1 mg/kg. Two days later, serum calcium diminished to normal levels, and remained within normal range during 12 mo follow-up. CONCLUSION: Pamidronate appears to be effective in paediatric patients with WBS and hypercalcaemia.     

Subcutaneous fat necrosis of the newborn: hypercalcaemia with hepatic and atrial myocardial calcification

Subcutaneous fat necrosis of the newborn (SCFN) is a very rare disorder, which can be complicated by hypercalcaemia and thrombocytopenia. The case is presented of an infant with SCFN and symptomatic hypercalcaemia, who developed calcifications in the liver, the inferior vena cava, and the atrial septum of the heart. The hypercalcaemia was treated with hyperhydration, frusemide, glucocorticoids, and a diet low in calcium and vitamin D. Clinical features, diagnosis, complications, and treatment of this rare condition are discussed.     

Prednisolone and cellulose phosphate treatment in idiopathic infantile hypercalcaemia with nephrocalcinosis

Abstract: A girl presented at the age of 8 months with idiopathic infantile hypercalcaemia complicated by hypercalciuria, nephrocalcinosis and failure to thrive. Her hypercalcaemia was partially corrected by prednisolone, but resolved with the addition of cellulose phosphate. Her height and weight showed significant improvement during the treatment period. Cellulose phosphate should be considered in the management of children with idiopathic infantile hypercalcaemia and nephrocalcinosis.     

Indomethacin responsive hypercalcaemia associated with a renal sarcoma.

An infant presented with a non-metastatic renal spindle cell sarcoma and hypercalcaemia, which resolved after treatment with indomethacin. There was in vivo and in vitro evidence that hypercalcaemia was mediated by circulatory prostaglandins.     

Hypercalcaemia in cerebellar medulloblastoma: pathogenesis of solid tumour-associated hypercalcaemia

A 7-year-old boy developed acute, severe hypercalcaemia following the partial excision of a cerebellar medulloblastoma. The serum calcium level was extremely high (19.8 mg/100 ml), but a skeletal survey revealed no apparent bone metastatic lesions; such lesions were only detected by X-ray 3 weeks after the onset of hypercalcaemia. Hypercalcaemia was promptly resolved by intravenous mithramycin administration, before which the serum parathyroid hormone level, 1,25-(OH)₂-vitamin D level and the nephrogenous cyclic AMP level were low. However the relation between serum calcium levels and urinary calcium excretions indicated that renal calcium reabsorption was increased in association with hypercalcaemia, suggesting that a parathyroid hormone-like effect was operative on the renal tubules. It is possible that a combination of increased bone resorption by metastatic tumour cells and renal tubular handling of calcium presumably mediated by tumour-produced humoral factors was responsible for the acute development of severe hypercalcaemia in this patient with medulloblastoma.Abbreviations PTH parathyroid hormone - HHM humoral hypercalcaemia of malignancy     

A symptomatic female patient with Duchenne muscular dystrophy diagnosed by dystrophin-staining: A case report

We report a case of symptomatic carrier of Duchenne muscular dystrophy (DMD) in a 14-year-old girl with no prior family history of DMD. She presented with chest pain, enlarged calf muscles, an elevated serum creatine kinase (CK), and decreased left ventricular function. Histological examination of skeletal muscle revealed myopathic changes and immunostaining with anti-dystrophin antiserum demonstrated a mosaic pattern which are compatible with the observations in carriers of DMD. Southern blots using the dystrophin cDNA revealed no evidence of a deletion within the DMD gene in the patient or in her mother. We found this observation interesting for two reasons: 1. Cardiomyopathy is rare in female DMD patients. 2. Immunostaining of a muscle biopsy with anti-dystorphin serum proved to be valuable in the diagnosed for symptomatic carriers of the dystrophin gene mutation.     

Vitamin D intoxication and hypercalcaemia in an infant treated with pamidronate infusions

Bisphosphonates are used for the treatment of childhood hypercalcaemia, especially that due to malignancies. Here we report the use of intravenous pamidronate for the treatment of hypercalcaemia due to vitamin D intoxication in a 3-month-old infant. Serum calcium levels were normalised without complications. Conclusion:pamidronate may be used in hypercalcaemia due to vitamin D intoxication in paediatric cases resistant to hydration, diuretics or corticosteroids.     

Idiopathic infantile hypercalcaemia--a continuing enigma.

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition.     

Hypercalcaemia: An Unusual Complication of Tuberculosis. A Case Report

Hypercalcaemia: An unusual complication of tuberculosis. A case report. Severe hypercalcaemia was observed in a seven year old Noumean boy with mediastinal lymph node tuberculosis. Many therapeutic manoeuvres were employed initially to obtain control of the serum calcium level, which finally responded to a course of indomethacin and remained stable on prednisone and antituberculous drug therapy. It has been postulated that the hypercalcaemia is due to increased sensitivity to Vitamin D, as seen in patients with sarcoidosis, but it is suggested that prostaglandin secretion from the inflammatory tissue may contribute to the hypercalcaemia.     

Hypercalcaemia in osteogenesis imperfecta treated with pamidronate

Accepted 10 September 1996The response to the bisphophosphonate, pamidronate, is reported in a child with osteogenesis imperfecta who had recurrent symptomatic hypercalcaemia after immobilisation following fractures. Oral clodronate was effective in the prevention of immobilisation hypercalcaemia in the same child. The bisphosphonates may have other roles in osteogenesis imperfecta by decreasing bone turnover.     

Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant condition due to heterozygous loss of function calcium sensing receptor (CaSR) mutations. However, individuals who are homozygous for CaSR mutations have neonatal severe hyperparathyroidism (NSHPT), which unlike the relatively benign and asymptomatic FHH can be fatal without parathyroidectomy. We report three patients with NSHPT associated with marked hypercalcaemia and severe hyperparathyroidism with related skeletal demineralisation. We describe the novel use of intravenous pamidronate in NSHPT, to control severe hypercalcaemia in these patients prior to parathyroidectomy and in one individual as a rescue therapy to stabilise life-threatening demineralisation. Furthermore, a marked phenotypic heterogeneity was observed amongst four members from a large kindred with the same homozygous CaSR mutations: one patient would have died without parathyroidectomy in infancy; a second patient survived infancy but underwent parathyroidectomy in early childhood following severe symptomatic hypercalcaemic episodes; whilst the other two patients have survived to adolescence without parathyroidectomy. Additionally, in contrast to the literature these two individuals suffered minimal morbidity. Conclusion:we commend the short-term use of pamidronate in neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt hyperparathyroid-driven skeletal demineralisation in preparation for parathyroidectomy. The remarkable degree of phenotypic variation demonstrated remains unexplained without functional studies; this variability highlights the challenge of treating this rare condition.Abbreviations CaSR calcium sensing receptor - FHH familial hypocalciuric hypercalcaemia - NSHPT neonatal severe hyperparathyroidism - PTx parathyroidectomy     

Hypercalcaemia in osteogenesis imperfecta treated with pamidronate

The response to the bisphosphonate, pamidronate, is reported in a child with osteogenesis imperfecta who had recurrent symptomatic hypercalcaemia after immobilisation following fractures. Oral clodronate was effective in the prevention of immobilisation hypercalcaemia in the same child. The bisphosphonates may have other roles in osteogenesis imperfecta by decreasing bone turnover.