Fahr´s Syndrome; Pseudohypoparathyroidism Type Ib Masquerading as Epileptic Seizures.

Hypocalcaemia of various origin can be manifested by paresthesia, muscle cramps, muscle weakness, syncope, convulsions and even severe psychomotor retardation. Such symptoms can be initially considered as signs of epilepsy. We present a 12- year old boy with partial seizures and basal ganglia calcifications, initially diagnosed as having Fahr´s disease and epilepsy, where severe hypocalcaemia, due to genetically confirmed pseudohypoparathyroidism type Ib was the underlying cause. Excellent clinical improvement was observed after calcium and vitamin D therapy. The basal ganglia calcifications were secondary due to chronic hypocalcaemia, therefore the appropriate diagnosis was pseudohypoparathyroidism type Ib with Fahr´s syndrome, but not Fahr´s disease. In conclusion, the serum evaluation of minerals, especially calcium and phosphate, should be performed in all patients with convulsions, cramps and psychomotor retardation. This is essential in arriving at a proper diagnosis and early initiation of appropriate treatment.

Three different causes of hypercalciuria.

Hypercalciuria is defined as urinary calcium excretion ≥0.1 mmol/kg/24 h, and can be a result of various disease states. The most frequent clinical signs of hypercalciuria include hematuria, abdominal pain, urolithiasis, nephrocalcinosis, dysuria, enuresis, and urinary tract infection. 3 case reports of children with hypercalciuria of different origin are presented, with final diagnoses of (1)idiopathic hypercalciuria, (2)familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and (3)metabolic bone disease of prematurity, respectively. Assessment of hypercalciuria is essential in all children with urolithiasis and nephrocalcinosis, or demineralization of bone. It should be also a part of differential diagnostic procedure in hematuria, recurrent abdominal pain, urinary tract infection and enuresis in childhood.

Idiopathic infantile hypercalcaemia in 5-month old girl.

Idiopathic infantile hypercalcaemia (IIH) is a mineral metabolism disorder of unknown origin. It is characterized by high levels of serum calcium resulting in parathyroid hormone (PTH) suppression, muscle hypotonia, thirst, anorexia, failure to thrive, psychomotor retardation, constipation, nephrocalcinosis. Treatment consists of low calcium diet, glucocorticoids, furosemide. We present a case of 5-month old girl with IIH, where total calcaemia peaked to 4.25 mmol/l. The leading symptoms were failure to thrive, constipation, muscle hypotonia, dehydration. Rehydration, low calcium diet, and application of glucocorticoids and furosemide resulted in a drop in calcaemia to normal values and an overall clinical improvement within two weeks. Williams-Beuren syndrome (WBS), benign familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT), Jansen's metaphyseal dysplasia, primary hyperparathyroidism, vitamin D intoxication, granulomatous diseases, thyroid disease, malignancy were all ruled out. In conclusion, infants with failure to thrive should have their serum levels of minerals, especially, calcium, checked. In case of hypercalcaemia, treatment with corticosteroids and furosemide should be initiated, together with further diagnostic steps in order to elucidate its origin.

Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity in children with vesicoureteral reflux.

OBJECTIVES: The aim of this study was to measure U-NAG in children with vesicoureteral reflux (VUR) and examine the relationship between selected clinical parameters. BACKGROUND: U-NAG/creatinine ratio is a marker of renal tubular impairment and an increase in this ratio have been reported to affect the kidneys in various diseases. METHODS: The U-NAG/creatinine ratio was measured in the spot urine of 22 children (10 boys and 12 girls, mean age 2.83 +/- 2.42 years) with VUR. In 8 patients The VUR was unilateral grade I-IV (8 patients), and it was was bilateral, grade I-V in 14 patients. In patients with bilateral reflux and different VUR grade on each side, the highest grade of VUR was taken into consideration. RESULTS: The U-NAG/Cr levels were significantly higher in VUR patients compared to the reference (p = 0.0001). There was no difference in U-NAG/Cr between children with unilateral (n = 8) and bilateral (n = 14) VUR (p = 0.66). There was no difference in U-NAG/Cr between patients with VUR grades I-III and IV-V (p = 0.67). The U-NAG/Cr activity was higher in patients with reflux nephropathy (RN; n = 9) when compared to reference data (p = 0.0001), however there was no difference in comparison to children without RN (p = 0.84). CONCLUSIONS: U-NAG/Cr increased in children with VUR grade I-V and there is a very weak relationship with the grade of VUR. U-NAG/Cr is a useful marker of renal tubular impairment, however there is poor relationship with the degree of kidney damage in patients with VUR (Tab. 1, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

Quantitative ultrasonometry of the calcaneus in children with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate bone quality by means of quantitative ultrasonometry (QUS) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy children [37 with oligoarticular JIA, mean age (+/-s.d.) 10.54 +/- 3.42 yr; and 33 with polyarticular rheumatoid factor negative JIA, mean age (+/- s.d.) 11.33 +/- 2.88 yr] were enrolled. Quantitative ultrasonometry was measured on both heels with a Cuba Clinical portable device. Body height, weight and body mass index were recorded together with disease duration and cumulative dose of prednisone. RESULTS: The lowest QUS parameters were observed in children with polyarticular JIA (P< 0.001 and 0.01 when compared with reference data and oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS values were also significantly lower in comparison with the reference data (P< 0.002). The QUS parameters were strongly influenced by body height, and to a lesser degree by body weight. In children with polyarticular JIA, there were significant inverse correlations between QUS parameters and disease duration [r=-0.57, P< 0.01 for broadband ultrasound attenuation (BUA) and r = - 0.67, P< 0.01 for velocity of sound (VOS)]. Similarly, there were inverse correlations between QUS and cumulative dose of prednisone (r = - 0.48, P< 0.05 for BUA and r =- 0.50, P < 0.01 for VOS, respectively). Similar results were obtained when BUA and VOS were adjusted for height. CONCLUSIONS: Disease duration and cumulative dose of prednisone in children with polyarticular JIA are risk factors of stunted growth and decreased QUS values of bone quality.

Pseudohypoparathyroidism type IA and II with severe neuropsychic manifestations.

Pseudohypoparathyroidism (PHP) is characterized by unresponsiveness of target tissues to the biological actions of the parathyroid hormone (PTH), with resulting hypocalcemia and hyperphosphatemia, despite the elevated serum levels of PTH. PHP is divided into types Ia, b, c and II, depending on the presence of Albright's hereditary osteodystrophy (AHO), defective urinary excretion of phosphate (U-P) and response in urinary excretion of cyclic adenosine monophosphate (U-cAMP) after the administration of exogenous PTH. Patients with PHP might exhibit various manifestations of neuropsychic disturbances. We present two boys, aged 14 and 16 years, both with paresthesia, anxiety and epilepsy; the former patient also suffered from mild mental retardation. In both patients, hypocalcemia and hyperphosphatemia together with increased serum levels of PTH suggested the diagnosis of PHP. After administration of exogenous PTH (Ellsworth-Howard test), there was a drop in U-P in both patients, while U-cAMP was decreased in the first patient and increased in the second one, thus confirming the diagnoses of PHP Ia and II, respectively. Neuropsychic disturbances and epilepsy resolved completely in both patients after treatment with calcium and dihydrotachysterol. Evaluation of calcemia and phosphatemia should be mandatory in all patients with neuropsychic disorders. Ellsworth-Howard test remains a useful tool in the differential diagnosis of PHP.

Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice.

Previous studies have shown that 60-70% of variance in peak bone density is determined genetically. The higher the peak bone density, the less likely an individual is to eventually develop osteoporosis. Therefore, the amount of bone accrued during postnatal and pubertal growth is an important determining factor in the development of osteoporosis. We evaluated the contribution of skeletal changes before, during, and after puberty to the development of peak bone density in C3H/HeJ (C3H) and C57BL/6J (B6) mice. Volumetric bone density and geometric parameters at the middiaphysis of femora were measured by peripheral quantitative computed tomography (pQCT) from days 7 to 56. Additionally, biochemical markers of bone remodeling in serum and bone extracts were quantified. Both B6 and C3H mice showed similar body and femoral weights. B6 mice had greater middiaphyseal total bone area and thinner cortices than did C3H mice. Within strains, males had thicker cortices than did females. C3H mice accumulated more minerals throughout the study, with the most rapid accumulation occurring postnatally (days 7-23) and during pubertal maturation (days 23-31). C3H mice had higher volumetric bone density as early as day 7, compared with B6 mice. Higher serum insulin-like growth factor I (IGF-I) was present in C3H mice postnatally at day 7 and day 14. Until day 31, B6 male and female mice had significantly higher serum osteocalcin than C3H male and female mice, respectively. Alkaline phosphatase (ALP) was found to be significantly higher in the bone extract of C3H mice compared with B6 mice at day 14. These data are consistent with and support the hypothesis that the greater amount of bone accrued during postnatal and pubertal growth in C3H mice compared with B6 mice may be caused by increased cortical thickness, increased endosteal bone formation, and decreased endosteal bone resorption.

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity. Deletions of 11p11-p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 and PFM. Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS.

Ultrasound parameters of calcaneal bone density in girls with anorexia nervosa.

Osteoporosis is common in patients with anorexia nervosa (AN), but ultrasound has so far been scarcely used to detect it We measured calcaneal broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 26 AN girls (mean age 15.1+/- 1.5 years) using a Cuba Clinical device (McCue Ultrasonics, UK). Basic anthropometric (body weight, height and body mass index--BMI) and clinical data (mean duration of AN, number of absent cycles, weight loss) were collected. All of the girls reported that they did at least one hour's vigorous exercise a day. BUA was significantly lower (p<0.004) and VOS significantly higher (p<0.0001) in comparison with reference data. Body weight and BMI at the time of the measurements were significantly lower than the reference data (p<0.0001). There were no correlations between body weight or height and BUA or VOS, but there was a slight correlation between BUA and BMI (r=0.4, p<0.05) and a slight inverse correlation between VOS, body weight and BMI (r=-0.48 and r=-0.43, p<0.01). VOS slightly correlated with weight loss (r=0.4, p<0.05), significantly with the weekly number of exercise hours (r=0.48, p<0.01). The duration of AN, the number of missed cycles and the percentage of weight loss did not correlate with BUA, and neither the duration of AN nor the number of missed cycles correlated with VOS. The low BUA value could be attributed to poor nutrition, and substantial physical activity may lead to the increase in VOS. In conclusion, girls with AN have low BUA and high VOS values, neither of which correlate with the duration of AN or the number of missed cycles.

Comparison of bone formation responses to parathyroid hormone(1-34), (1-31), and (2-34) in mice.

In this study we used a mouse model system to compare the in vivo effects of parathyroid hormone(1-34) [PTH(1-34)] with that of PTH(1-31) or PTH(2-34) analogs. Daily subcutaneous administration of PTH(1-34) for 15 days caused a dose-dependent increase in the serum osteocalcin level and bone extract alkaline phosphatase activity, markers of bone formation. PTH(2-34) was much less potent, whereas PTH(1-31) was equipotent in stimulating bone formation parameters in mice. PTH(1-34) caused significant increases in serum calcium (after 4 h) and tartrate-resistant acid phosphatase activity in bone extract (after 4 h), whereas PTH(2-34) and PTH(1-31) were less potent. Because PTH(1-31) caused a smaller increase in bone resorption parameters compared to PTH(1-34), despite similar effects on bone formation parameters, we evaluated the long-term anabolic effects of PTH(1-31) and PTH(1-34) in mice. Weekly evaluations of serum osteocalcin levels demonstrated that daily injections of PTH(1-34) and PTH(1-31) at 80 microg/kg body weight increased serum osteocalcin levels within 1 week of the start of treatment, which were maintained during the entire 22 week treatment. Assessment of bone density at the end of the treatment period with peripheral quantitated computed tomography (pQCT) revealed that PTH(1-34) caused a significantly greater increase in femoral bone density compared to PTH(1-31) at the middiaphysis (18% vs. 9% over vehicle control; p < 0.001). Both PTH(1-34) and PTH(1-31) increased periosteal circumference compared to vehicle (p < 0.01) without a significant difference between the two treatments. In contrast, PTH(1-34) caused a significantly greater reduction in endosteal circumference than PTH(1-31) (p < 0.001). Both analogs significantly increased maximum load and area of moment of inertia over the vehicle group. In conclusion, our findings suggest that PTH(1-34) and PTH(1-31) may exhibit different anabolic effects at the periosteum vs. endosteum in the long bones of mice.

Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading.

Although C3H/HeJ (C3H) and C57BL/6J (B6) mice are similar in body size (and adult weight), and have bones of similar external size, C3H mice have higher peak bone densities than B6 mice (e.g., 53% higher peak bone density in the femora). The current studies were intended to assess the role of mechanical loading/unloading as a possible determinant of the bone density difference between these inbred strains of mice and, specifically, to assess the effect of sciatic neurectomy on histomorphometric indices of bone formation and resorption in the tibiae of female C3H and B6 mice. Groups of 10 mice of each strain were subjected to left-side sciatic neurectomy (left hindlimb immobilization) or a sham procedure. The contralateral (right) legs of each mouse were used as controls. Four weeks of immobilization produced no systemic changes in bone formation indices in either strain of mice (i.e., no change in serum alkaline phosphatase or serum osteocalcin). However, histomorphometric assessments at the tibiofibular junction showed that 4 weeks of immobilization caused a time-dependent decrease in the length of the endosteal bone forming perimeter (e.g., 14% of control single-labeled, noneroded surface at 4 weeks, p < 0.005) with a concomitant increase in the length of the endosteal bone resorbing perimeter (i.e., 424% of control eroded surface at 4 weeks, p < 0.005), in the B6 mice. These effects were associated with an increase in medullary area (132% of control, p < 0.05) at this site, in the B6 mice. The pattern of response was different in the tibiae of the C3 mice-a much smaller decrease in bone forming perimeter (88% of control at 4 weeks, p < 0.05), with no associated increase in bone resorbing perimeter, and no change in medullary area. Similar effects were seen at a second cross-sectional sampling site, in the proximal tibia. Together, these findings indicate that B6 mice are more sensitive to endosteal bone loss from hindlimb immobilization than C3H mice.

Transient hyperphosphatasemia--where do we stand?

Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by transiently increased serum activity of alkaline phosphatase (S-ALP), predominantly its bone or liver isoform, in children under five years of age. There are no signs of metabolic bone disease or hepatopathy corresponding with the increased SALP, nor is there a disease common to all children with THI. To date, THI has been reported in more than 400 children. Viral etiology of THI has been proposed; transiently increased bone turnover and impaired clearance of ALP from the serum were originally considered as its causes. The pathogenesis is most probably multifactorial. THI is a benign disorder, as prospective follow-up of children with a history of TH revealed normal growth and normal bone density. Children with TH should be spared from excessive diagnostic procedures.

Foramina parietalia permagna: report of nine cases in one family.

Nine members of a family with foramina parietalia permagna (FPP), inherited as an autosomal dominant trait are reported. Although usually benign, FPP may be associated with other malformations.

Ultrasound transmission through the Os calcis in children: which side should we measure?

Ultrasound measurement of the os calcis is a promising technique when evaluating bone status. Large individual differences between the right and left calcaneus in adults were reported. In this study, calcaneal acoustic parameters in 373 healthy children and adolescents were investigated using a CUBAClinical bone densitometer. No significant difference was found between mean values on the right and left foot, however, individual difference in broadband ultrasound attenuation was 11 +/- 9.25%. Individual differences between both sides in ultrasound investigation of the os calcis should not be underscored either in adults or in children.

[Magnesium, its role and metabolism]. / Magnezium, jeho úloha a metabolismus.

Magnesium (Mg) is the fourth most abundant cation in the human body and is second only to potassium in intracellular metabolism. Magnesium deficiency results in biochemical, neuromuscular and cardiovascular changes. This review deals with both normal and abnormal Mg metabolism.