A case of idiopathic basal ganglia calcification associated with membranoproliferative glomerulonephritis

Idiopathic basal ganglia calcification (IBGC) is a syndrome in which bilateral cerebral calcification occurs despite the absence of abnormal calcium metabolism. A 17-year-old Japanese female was admitted for investigation of intermittent proteinuria from the age of 12 years. On admission, her blood pressure was 126/60 mmHg and her serum creatinine was 0.8 mg/dL. Although computed tomography revealed bilateral striopallidodentate calcinosis, her level of intelligence and neurological findings were normal, as were the results of endocrine tests including parathyroid hormone. Asymptomatic IBGC was diagnosed. Renal biopsy showed membranoproliferative glomerulonephritis. Peritoneal dialysis was started for end-stage renal failure when she was 24 years old. Pyramidal and extrapyramidal signs started to develop at the age of 27 years and progressed, resulting in death from aspiration pneumonia at the age of 32 years. Post-mortem revealed bilateral calcification of the basal ganglia, dentate nucleus, thalamus, and centrum semiovale. On light microscopy, there was circumferential calcification of the media and intima of affected vessels in the brain, including small arteries, small veins, and capillaries, and luminal narrowing was seen. On electron microscopy, layers of differing electron density were arranged in concentric laminae. This is the first report of IBGC with bilateral and symmetrical cerebral calcification accompanied by membranoproliferative glomerulonephritis resulting in end-stage renal failure.     

BASAL GANGLIA CALCIFICATION IN POSTOPERATIVE HYPOPARATHYROIDISM

The presence of bilateral basal ganglia calcification was sought in nine patients with post-operative and two patients with primary hypoparathyroidism, using computerized axial tomography (CAT) and plain skull radiographs. Calcification was detected with CAT in seven patients; five with post-operative and both with primary hypoparathyroidism, but in only one was it demonstrable on plain X-ray films. The presence of calcificaton appeared to be related to the duration of the disease and possibly the degree of control of serum calcium. Six of the seven patients with cerebral calcification also had cataracts. The incidence of basal ganglia calcification in hypoparathyroidism is probably much greater than previously recognized, especially in post-operative hypoparathyroidism.     

HIV encephalopathy in a child in the presence of a high CD4 count: a rare presentation

A two-year-old girl presented with regression of developmental milestones for the last three and a half months. She was diagnosed as HIV-positive, but her CD4 count was found to be normal. Computed tomography (CT) scan of her brain showed bilateral basal ganglia calcification with cortical atrophy. A final diagnosis of HIV encephalopathy was made which had occurred despite a normal CD4 count, which is extremely uncommon.     

Extensive soft tissue calcification (calcinosis universalis) in systemic lupus erythematosus.

A 21-year-old woman with long-standing systemic lupus erythematosus developed extensive calcification of the soft tissues of the thoracic and abdominal walls and extremities early in her illness, and these calcifications gradually disappeared over the course of her disease. The extent of this calcinosis and apparent spontaneous regression are unusual events in systemic lupus erythematosus.     

Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis.

Familial hypoparathyroidism is an unusual and genetically heterogeneous group of disorders that may be isolated or may be associated with congenital or acquired abnormalities in other organs or glands. We have evaluated a family with a novel syndrome of autosomal dominant hypoparathyroidism, short stature, and premature osteoarthritis. A 74-yr-old female (generation I) presented with hypoparathyroidism, a movement disorder secondary to ectopic calcification of the cerebellum and basal ganglia, and a history of knee and hip replacements for osteoarthritis. Two members of generation II and one member of generation III were also documented with hypoparathyroidism, short stature, and premature osteoarthritis evident as early as 11 yr. Because of the known association between autosomal dominant hypoparathyroidism and activating mutations of the calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing of PCR-amplified genomic DNA revealed a leucine to valine substitution at position 616 in the first transmembrane domain of the CaR, which cosegregated with the disorder. However, this amino acid sequence change did not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration in the coding region of the CaR gene was identified, but is not conclusively involved in the etiology of this novel syndrome. The cosegregation of hypoparathyroidism, short stature, and osteoarthritis in this kindred does suggest a genetic abnormality involving a common molecular mechanism in parathyroid, bone, and cartilage.     

Mechanism of intracerebral calcification in hypoparathyroidism

The mechanism of intracranial calcification in hypoparathyroidism, more frequently seen in pseudo--than idiopathic hypoparathyroidism, has not been completely elucidated, but may be related more to the duration of hypocalcaemia and hyperphosphatemia than parathyroid hormone itself. Hyperphosphatemia promotes ectopic calcification, especially in blood vessel and periarticular tissue in renal failure, but in brain tissue in hypoparathyroidism. Participation of PTH receptor2 in the brain and superoxide production by mitochondria in hypoparathyroidism should be explored with reference to intracerebral calcification and neurodegenerative diseases.     

Surgical management of calcinosis cutis universalis in systemic lupus erythematosus

Calcinosis cutis is common in several connective tissue diseases but rare in systemic lupus erythematosus (SLE). A 43-year-old woman with a 12-year history of SLE who presented with calcinosis cutis at the time of SLE diagnosis developed a large, ulcerated, draining mass on her left hip. The lesion was excised and skin was grafted, with an excellent early result. The clinical variants and mechanisms of ectopic calcification are discussed, as well as the proposed medical therapies for calcinosis cutis.     

Endocrine dysfunction in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found.     

Reading epilepsy as the initial symptom of idiopathic hypoparathyroidism

Reading epilepsy is a rare form of reflex epilepsy that occurs exclusively during reading. In this report, we describe a patient in whom seizure was the initial symptom of idiopathic hypoparathyroidism. A 31-year-old man experienced seizures three times in different bookshops while browsing. Chvostek's sign was observed. Serum calcium and parathyroid hormone levels were decreased. Brain computed tomography revealed symmetrical calcification at the dentate nuclei of the cerebellum and the basal ganglia. The interictal electroencephalography was normal. There was no photoparoxysmal response. After amelioration of serum calcium level with oral administration of vitamin D, seizure attacks ceased without antiepileptic drugs. This case is, to our knowledge, the first report of reading epilepsy associated with hypocalcemia due to idiopathic hypoparathyroidism. The psychological stress of reading at bookshops without buying might have triggered seizures under CNS hyperexcitability due to hypocalcemia.     

An autopsy case of infantile GM1 gangliosidosis with adrenal calcification

We describe an autopsy case of a 1-year-old male baby presenting with failure to gain milestones, floppiness, and reddish skin lesions since birth. Fundoscopic examination revealed bilateral cherry-red spots in the macula. The baby died of respiratory failure and autopsy revealed numerous ballooned neurons and astrocytes with cytoplasmic storage material seen throughout central white matter, basal ganglia, cerebellum, choroid plexus, and brain stem. There was neuronal degeneration with loss of myelin in central white matter with axonal degeneration as well. The storage material was weakly positive with PAS and oil red-O stains. Ultrastructurally, multilayered lamellated bodies were seen within the ballooned neurons. Biochemical analysis of lysosomal enzymes done in leucocytes revealed β-galactosidase deficiency that is consistent with GM1 gangliosidosis. Extensive visceral deposition of similar material was also seen. Remarkably, both adrenals revealed extensive medullary calcification, which has not been reported in this lysosomal storage disorder, to the best of our knowledge.     

Mobile intracardiac calcinosis: a new risk of thromboembolism in patients with haemodialysed end stage renal disease

Cardiac calcinosis is a common complication of end stage renal disease. A newly observed risk of thromboembolism is reported in four patients with mobile cardiac calcinosis, treated with long term dialysis. Rapidly growing mobile calcification was confirmed by echocardiography. Each patient had an imbalance in serum calcium × inorganic phosphate (Ca × P product  50); this imbalance could not be treated due to the sudden death of the patient or the need for surgical resection to prevent recurrent cerebral thromboembolism. Histological examination revealed intracardiac calcinosis in three cases, and each case showed haemodialysis hypoparathyroidism (intact PTH < 160 pg/ml). Thromboembolism in such cases is rare, however it indicates a need for cautious echocardiographic monitoring in end stage renal disease in patients with an uncontrolled Ca × P product.


Keywords: cardiac mass; intracardiac mobile calcinosis; haemodialysis hypoparathyroidism; thromboembolism; end stage renal disease     

Severe cerebral calcification in a case of LEOPARD syndrome

We report severe brain calcification in a case of LEOPARD syndrome that has not been reported in the literature. A 53-year-old Japanese man presented with generalized lentigines, arrhythmia, gonadal hypoplasia, endocrine abnormality, mental retardation and skeletal abnormalities, and was consequently diagnosed as LEOPARD syndrome. Brain computed tomography demonstrated surprisingly dense and symmetric calcifications in the cerebellar dentate nuclei, cerebral basal ganglia, thalamus, and cerebral white matter. It may be an incidental idiopathic calcification. Alternatively it may be a rare clinical manifestation of LEOPARD syndrome.     

Relapsing polychondritis with idiopathic hypoparathyroidism]

A 49-year-old man who had been treated with vitamin D since idiopathic hypoparathyroidism (IPH) was diagnosed at age 15 was referred to our hospital because of progressive wheezing. The same condition was also diagnosed in his sister at age 19. Chest radiography and computed tomography (CT) showed diffuse tracheal stenosis to a diameter of 6-8 mm. Laryngoscopy revealed no abnormality in the patient's epiglottis or vocal cords. No intact parathyroid hormone was detected in his sera but a brain CT scan showed calcification of the basal ganglia, which was compatible with IPH. Steroid therapy relieved his wheezing occasionally, but with little improvement of the narrowing of his trachea. He died of respiratory failure accompanied by lung abscess 15 weeks later. Autopsy revealed tracheal stenosis, thickening of the tracheal wall with marked fibrosis, and slight infiltration of inflammatory cells, which supported a diagnosis of relapsing polychondritis. This is the first report of relapsing polychondritis associated with IPH. Since both diseases are associated with autoimmune activity, this case may provide some insight into the pathogeneses of both diseases.     

特发性甲状旁腺功能减退症22例颅脑病变的CT诊断

目的探讨特发性甲状旁腺功能减退症的颅脑病变特点及CT诊断要点。方法收集22例甲状旁腺功能减退症患者的颅脑cT资料,总结分析诊断要点。结果甲状旁腺功能减退症的颅脑CT多表现为典型区域的对称性钙化,但部分患者早期病变钙化不典型。结论cT诊断甲状旁腺功能减退症颅脑病变的价值优势值得肯定。     

Calcinosis of joints and periarticular tissues associated with vitamin D intoxication.

We describe a patient with rheumatoid arthritis and widespread joint and periarticular calcinosis related to self-medication with vitamin D, which was aggravated by oral phosphate therapy prescribed for her hypercalcaemia. Hydroxyapatite was shown in the synovial fluid from affected joints. The role played by tissue injury in the pathogenesis of soft tissue calcification is discussed.     

Multimodal imaging in the differential diagnosis of soft tissue calcinosis

Soft tissue calcinosis is a common radiographic finding, which may be related to different types of pathological processes. Multimodality imaging, combined with analysis of clinical and laboratory data, plays an important role for the differential diagnosis of these conditions. Conventional radiography is considered the first line approach to soft tissue calcinosis; CT and MRI may provide further information to better characterize calcified deposits. Imaging may help to distinguish metabolic calcification, such as primary tumoral calcinosis and the secondary one (associated with acquired disorders of calcium or phosphate regulation), from dystrophic calcification, which is associated to normal blood values of phosphate. The sedimentation sign typical of tumoral calcinosis has been demonstrated by plain film radiography, CT, MRI, and, more recently, by ultrasonography. Other types of soft tissue calcinosis may have a degenerative, metaplastic or neoplastic origin, and their characterization strongly relies on multimodality imaging.     

Idiopathic hypoparathyroidism and celiac disease in two patients with previous history of cataract.

We report two patients with idiopathic hypoparathyroidism and celiac disease. Both had undergone surgery for cataract previously. The patients presented with tetany in the absence of gastrointestinal complaints. Investigations showed severe hypocalcemia, hypoparathyroidism, flattening of duodenal villi histologically, and diffuse cerebral and basal ganglia calcifications on CT scan. After a gluten-free diet with calcium supplementation, the clinical situation and biochemical values improved.     

Presence of spondyloarthropathy and its clinical profile in patients with hypoparathyroidism

Background Though spondyloarthropathy has been described in patients with sporadic idiopathic hypoparathyroidism (SIH), the clinical profile is not known. Objectives To describe the clinical profile including radiological features of spondyloarthropathy and prevalence of HLA‐B27 allele in patients with hypoparathyroidism, and to identify any differences from ankylosing spondylitis. Subjects and methods Clinical characteristics and radiographs of pelvis and spine were assessed in 40 consecutive patients with SIH. Radiographs were assessed by radiologist (RS) and rheumatologist (RG) for the features of spondyloarthropathy including sacroiliitis, syndesmophytes and hip joint calcification, and so on. HLA‐B27 genotyping was carried out in patients with SIH, and 195 healthy controls using duplex PCR. Fourteen control radiographs were from age‐matched normal individuals. Results Three patients with SIH had clinically overt spondyloarthropathy which closely resembled ankylosing spondylitis. Fourteen (eight females and six males) of the 40 patients with SIH showed radiological changes including syndesmophytes in lower dorsal or dorso‐lumbar spine (n = 6), sacroiliitis and new bone formation at the acetabular rim of the hip joint (n = 10). Though all six patients demonstrating syndesmophytes had new bone formation at hip, sacroiliitis was seen in only three of them. None of the 14 controls had syndesmophytes, sacroiliitis or hip joint calcification. The mean (SD) duration of illness (15·4 ± 8·7 vs. 6·5 ± 5·9 years, P < 0·01), BMI (24·1 ± 5·2 vs. 20·8 ± 3·7 kg/m², P = 0·04) and frequency of basal ganglia calcification was higher (100%vs. 57·7%, P < 0·01) in patients who showed changes of spondyloarthropathy in comparison to those without these changes. On multiple logistic regression analysis, only duration of hypoparathyroid illness was associated with spondyloarthropathy with an odds ratio of 1·17 (95% CI = 1·05–1·30, P < 0·01) per year increase in the duration. The mean age, serum total calcium, inorganic phosphorus and serum intact PTH (iPTH) levels were not significantly different between SIH patients with and without spondyloarthropathy. The frequency of HLA‐B27 allele was comparable between SIH and the control groups. Conclusions Thus, spondyloarthropathy is a distinct clinical entity in patients with SIH. Its salient clinical features include presence of syndesmophytes at the thoracic or thoraco‐lumbar spine, mild sacroiliitis, calcification at the acetabular margin of hip, preserved bone density, equal distribution in both sexes and lack of HLA‐B27 association. Presence of spondyloarthropathy, like basal ganglia calcification, is associated with longer duration of hypoparathyroidism. It is important to differentiate hypoparathyroid‐related spondyloarthropathy from ankylosing spondylitis because the management for the two disorders is different.     

Hypoparathyroidism and pseudohypoparathyroidism

The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives.     

Tumoral calcinosis: New insights for the rheumatologist into a familial crystal deposition disease

A growing body of evidence points to extraosseous calcification (calcification occurring in nonosseous tissues) as a major cause of morbidity and mortality in humans. The term familial tumoral calcinosis encompasses a number of rare recessive diseases, often associated with increased reabsorption of phosphate through the renal proximal tubule, which manifests with periarticular or acral calcium deposition. Recently, the molecular pathogenesis of this group of disorders has been elucidated, leading to the identification of several proteins playing pivotal roles in the regulation of extraosseous calcification. This report reviews these advances as well as the potential implications of these discoveries for the management of acquired conditions associated with abnormal calcification.