K. Kruse

Calcium metabolism in Williams-Beuren syndrome

Increased 1,25-dihydroxyvitamin D levels and decreased basal and calcium-stimulated calcitonin serum levels have been found in children with Williams-Beuren syndrome (WBS). To determine whether isolated or combined disturbances of secretion or action of the calcium-regulating hormones may cause the tendency to hypercalcemia in WBS, we investigated several aspects of calcium metabolism in 27 normocalcemic children and adults, aged 2 to 47 years, with WBS. With the exception of slightly decreased 25-hydroxyvitamin D and slightly increased calcitonin in serum, all measured basal indexes of calcium and bone metabolism, including the serum levels of intact parathyroid hormone and 1,25-dihydroxyvitamin D, were comparable to control values. Total and extractable calcitonin, the latter representing the monomeric and biologically important form of the hormone, showed the same relative increase after a low-dose calcium infusion in patients and control subjects, indicating a normal capacity of the calcitonin-producing C cells of the thyroid gland in WBS. Furthermore, exogenous parathyroid hormone induced a normal response of 1,25-dihydroxyvitamin D, cyclic adenosine monophosphate, and phosphate excretion, indicating a normal response of the renal 25-hydroxyvitamin D-1 alpha-hydroxylase and the renal receptor-adenylate cyclase system to parathyroid hormone. These findings suggest that neither deficient calcitonin secretion nor increased renal sensitivity to parathyroid hormone is a feature of WBS in normocalcemic patients.

Hypocalcemic myopathy in idiopathic hypoparathyroidism

A girl with untreated idiopathic hypoparathyroidism presented with muscle weakness, depressed tendonreflexes and elevated serum creatine kinase. No morphological alterations of skeletal muscle or inhibition of muscle phosphorylase could be demonstrated. It is suggested that the myopathic symptoms may be due to functional changes of the muscle membrane during hypocalcemia.

Genetic heterogeneity of the ichthyosis, hypogonadism, mental retardation, and epilepsy syndrome

Major diagnostic criteria for the Rud syndrome are ichthyosis, hypogonadism, mental retardation, and epilepsy. Two unrelated patients are presented and compared with 28 reported cases.Genetical heterogeneity of the Rud syndrome is suggested by differences in clinical features, histological and endocrinological findings, steroid sulfatase activity, and modes of inheritance.

Serum alkaline phosphatase isoenzymes in epileptic children receiving anticonvulsant drugs

In 40 epileptic children on long-term anticonvulsant treatment, serum alkaline phosphatase (AP) isoenzymes were separated semiquantitatively using a combination of L-phenylalanine inhibition and heat inactivation. Though mean total serum AP activity was significantly increased compared to age matched controls, only 4 individual values exceeded the upper limit (mean + 2SD) of the reference sample. In epileptics the mean activity of the heat-sensitive non L-phenylalanine sensitive AP fraction (non-LPSAP) was significantly increased (P<0.01) and the mean Q-value (i.e. percentage ratio of heat-stable non-LPSAP/non-LPSAP) was significantly decreased (P<0.05), thus indicating an enhancement of the bone isoenzyme during anticonvulsant treatment. In 4 patients the isoenzyme pattern was abnormal although total serum AP activity was normal and in 3 of them the deviation indicated enhanced bone isoenzyme. The data provide evidence that in anticonvulsant treated children the bone isoenzyme, rather than hepatobiliary isoenzyme fraction, may be increased even when total serum AP activity is normal. Thus, semiquantitative separation of serum AP isoenzymes may be a helpful guide as to whether or not an epileptic child should be given vitamin D.

Parathyroid function and serum calcitonin in children receiving anticonvulsant drugs

Serum calcitonin (CT) levels and other aspects of calcium metabolism were investigated in 40 epileptic children receiving long-term treatment with phenytoin and/or other anticonvulsant drugs, and in 38 age-matched controls. In the patients CT levels were significantly lower. Immunoreactive parathyroid hormone (iPTH) was significantly elevated exceeding the upper limit of controls in 11 patients. We also observed a highly significant correlation between iPTH and urinary cyclic AMP (cAMP) excretion but a lack of such a correlation with the renal handling of phosphate; this indicates to us a dissociation between cAMP production and phosphaturia. A significant correlation between iPTH levels and urinary hydroxyproline excretion points to a normal action of PTH on bone in the patients. The low CT levels are not due to hypocalcemia and may be directly attributed to the effects of anticonvulsant drugs. As the primary effect of CT is a direct inhibition of PTH induced calcium loss from bone, the drug-related low CT levels in association with secondary hyperparathyroidism possibly is an additional factor in anticonvulsant bone disease.

Lymph node plasmacytoma in a child: Clinical and immunological findings with special reference to S-Ig and complement receptor subtypes

A ten year-old girl presented with increased susceptibility to infection, massive enlargement of the cervical lymph nodes, a high erythrocyte sedimentation rate and an extremely high serum IgA (peak level 66 g/l). The diagnosis of plasmacytoma was confirmed by the identification of a monoclonal immunoglobulin (IgAk) in the serum and in the plasma cells present in a cervical lymph node biopsy. Her disturbed blood coagulation and thrombelastogram, serum hyperviscosity, cryoglobulinemia, hyponatremia and constantly positive test for rheumatoid factor without evidence of rheumatic disease were attributed to the effects of the myeloma proteins. Other signs often associated with plasmacytoma (bone pain, osteolytic lesions, anemia, bone marrow failure or infiltration) were absent indicating that the plasmacytoma originated in a lymph node, which is unusual. This case is the second well-documented childhood plasmacytoma to be reported. With combined melphalan and prednisone therapy, the greatly enlarged lymph nodes regressed in size and the plasma IgA concentration fell to normal.Immunological investigations revealed a considerable reduction of blood T cells, and abnormal skin tests at the time of diagnosis indicated a disturbance of cellular immunity. There were also abnormalities in the B-cell system. The blood B lymphocytes were found to carry only complement receptors for C3b and mainly for IgA, whereas in normal individuals blood B cells bear complement receptors for both C3b and C3d and mainly surface Ig of the IgM class. In the lymph node biopsy, there were many primary follicles expressing complement receptors for both C3b and C3d among the dense plasma cell infiltrates, but germinal centers, which mainly serve to renew B cells, were completely absent.In conjunction with data from the literature, we concluded 1) that the production of normal B lymphocytes is blocked, probably due to a secondary T cell deficiency, and 2) that the majority of the residual blood and bone marrow B cells and the plasmacytoma cells are parts of the same neoplastic cell clone.

Hypercalciuria in Idiopathic Fanconi Syndrome

A 9 year old girl with idiopathic Fanconi syndrome and hypercalciuria is described. In order to determine whether the increased calcium excretion was directly or indirectly due to the disturbed phosphate metabolism, the behavior of the calcium excretion during therapy, the serum levels of 1,25-dihydroxyvitamin D and parathyroid hormone, and the effect of parathyroid hormone on the renal tubules were investigated. Normal serum 1,25-dihydroxyvitamin D and parathyroid hormone levels, lack of a correlation between the serum phosphate concentration and the degree of hypercalciuria, as well as unsuccessful therapy of the hypercalciuria with oral phosphate indicate that the increased calcium excretion cannot be explained by impaired renal phosphate reabsorption. The hypercalciuria in the patient was therefore regarded as being due to a primary decrease of tubular calcium reabsorption.