Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric study.

We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease.

Therapy-resistant seizures in pseudohypoparathyroidism. A case report.

A 30 year-old, mentally retarded female presented with uncontrolled seizures. The diagnosis of pseudohypoparathyroidism was established on grounds of clinical, laboratory and radiological evaluation. Despite normalization of serum calcium levels with vitamin D treatment, the patient continued to suffer from frequent convulsions. The possible pathogenesis of the therapy-resistant seizures and the therapeutic approach are discussed.

Linear growth in patients with hypophosphatemic vitamin D-resistant rickets: influence of treatment regimen and parental height.

The effects of different treatment regimens and the influence of parental height on the statural growth of 40 patients with hereditary vitamin D-resistant hypophosphatemic rickets were investigated. Three treatment regimens, each with oral phosphate, were used: vitamin D (0.5 to 2 mg/day), calcidiol (50 to 200 micrograms/day), and 1 alpha-hydroxyvitamin D3 (1 to 3 micrograms/day). Mean duration of follow-up was 9.5 +/- 5.1 years. The results show that (1) there was no acceleration of growth before puberty for the majority of children treated with vitamin D (12/16) or calcidiol (13/15), whereas 1 alpha-hydroxyvitamin D3 promoted catch-up growth in 10 of 16 patients; (2) height gain during puberty was normal, irrespective of the treatment; (3) most vitamin D-treated male and female subjects and calcidiol-treated male subjects had short adult stature, but the majority (75%) of the 1 alpha-hydroxyvitamin D3-treated groups had normal stature; (4) parental stature had little influence on the adult height of male subjects, but that of affected girls was positively correlated (p less than 0.002) with mid-parental height. These results demonstrate that 1 alpha-hydroxyvitamin D3 is superior to vitamin D or calcidiol for improvement of stature of patients with hypophosphatemic vitamin D-resistant rickets, and indicate the importance of parental height in determining the adult height of affected girls.

[Familial form of idiopathic hypercalciuria with nanism, bone and renal involvement in children]. / Forme familiale d'hypercalciurie idiopathique avec nanisme, atteinte osseuse et rénale chez l'enfant.

A brother and a sister are reported, demonstrating the severe form of childhood idiopathic hypercalciuria associated with dwarfism, renal defects and bone lesions (rickets and osteoporosis). The family are Israeli Beduins from a small village with a highly inbred population. The parents who are first cousins, and the remaining 6 siblings are not affected. This suggests an autosomal recessive form of transmission for the trait.

Spondyloepiphyseal dysplasia associated with progressive arthropathy. An unusual disorder mimicking juvenile rheumatoid arthritis.

A family is presented with three affected siblings suffering from a rare form of spondyloepiphyseal dysplasia with progressive arthropathy affecting most joints of the body except for the craniofacial skeleton. This syndrome, probably of autosomal recessive inheritance, clinically presents diffuse and chronic joint involvement and should be differentiated from juvenile rheumatoid arthritis and other rheumatic disorders.

Benign fibroepithelial polyps of the ureter and renal pelvis in childhood. Two case reports.

Benign fibroepithelial polyps of the ureter and renal pelvis are extremely rare in children. Two cases are presented and the clinical and surgical aspects of diagnosis and treatment are discussed.

The Weismann-Netter, Stuhl syndrome: a rare pediatric skeletal dysplasia.

A 5-year-old girl presented with lower limb deformities, delayed ambulation, short stature, facial dysmorphism and scoliosis. Radiologic examination showed severe anterior and external bowing of the femurs and anterior and internal bowing of the tibia and fibula, with posterior and medial cortical thickening. Square iliac wings, horizontal sacrum and low-set L5 were also seen. The diagnosis of Weismann-Netter, Stuhl syndrome was established with the exclusion of abnormalities in mineral and vitamin D metabolism. This rare skeletal dysplasia should be included in the radiologic differential diagnosis of congenital deformities of the lower extremities.

Pathophysiologic studies in idiopathic hypercalciuria presenting in childhood.

Idiopathic hypercalciuria (IH) was diagnosed in 11 children aged 5 3/12 to 10 6/12. Eight patients investigated 1-12 years later still had hypercalciuria. When compared to a control group of 10 healthy children, 5 patients demonstrated an excessive rise in urinary Ca excretion following an oral Ca load. These patients also demonstrated low urinary cAMP, normal serum iPTH and high normal iTCT levels. The remaining 3 patients responded normally to Ca loading, but otherwise showed similar metabolic findings as the above group. These findings suggest a hyperabsorptive mechanism for all our patients. The finding of relatively low values for TmP/GFR in most IH patients further suggests that here, as in many adult patients, this may be the primary pathogenic mechanism, causing low serum P, increased synthesis of 1,25 dihydroxyvitamin D and, thus, absorption of Ca. We believe this represents a physiologic variant state and not a disease state.

Multiple exostoses-mental retardation syndrome. A case report and review of the literature.

A girl seven years ten months of age with multiple exostoses-mental retardation (MEMR) syndrome was treated by bilateral supracondylar osteotomies at the age of six years 11 months for correction of severe genu valgum. The case is the 14th to be described in the English-language literature and seems to be the first on record in which the deformity was corrected by surgery. Typical findings in this syndrome include unusual facial features with bulbous nose, sparse scalp hair, large ears, microcephaly, mental retardation, cone-shaped epiphyses of the digital phalanges, and multiple exostoses. Each of these features may also appear in other constitutional and genetic disorders, and only their combination points to a definite diagnosis of MEMR syndrome. Other features, e.g., joint laxity and loose skin, are transient and may cause some confusion in diagnosis, sometimes leading to a mistaken diagnosis of cerebral palsy or Ehlers-Danlos syndrome. Thus, care must be taken in consecutive examinations to seek and identify each of the above mentioned typical features of the disorder.

Hypercalciuria as a cause of persistent or recurrent haematuria.

Of 91 children with idiopathic persistent or recurrent haematuria, eight also had hypercalciuria. This was transient in three and persistent in five. Persistent hypercalciuria was a rare cause of microscopic haematuria (two of 80), but common in association with gross haematuria (three of 11).

Pneumaturia: need for diagnostic alertness.

Pneumaturia, an air-filled urinary bladder with or without passage of gas in the urine, is a rare phenomenon in the general population, but is more frequent in defined high-risk subgroups. Relevant symptomatology may be hardly noticeable for a relatively long period; however, the outcome may be serious and sometimes fatal. We present three such cases and discuss diagnostic and therapeutic aspects.

A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition.

Direct measurement of TP/GFR: a simple and reliable parameter of renal phosphate handling.

As the Walton-Bijvoet nomogram for estimating renal phosphate (P) threshold (TmP/GFR) is not applicable to children of all ages, we sought an alternative method for measuring renal handling of P. Recognizing that the nomogram represents an indirect correlation between TmP/GFR and TP/GFR under fasting conditions, we examined this directly in 26 children. An excellent correlation was found, expressed as TmP/GFR = (fasting TP/GFR X 1.1) -0.3 (r = 0.95). The regression line in adults, expressed as TmP/GFR = (fasting TP/GFR X 1.4) -0.9 (calculated from published studies) is markedly different at the higher values typical for children. Since no advantage could be seen in the use of a mathematically derived TmP, we investigated the direct use of measured TP/GFR (tubular P reabsorption per 100 ml glomerular filtrate) as a measure of renal P handling in clinical practice. No differences were found between morning fasting and nonfasting values. Measurements in 151 healthy subjects aged 3 days to 53 years established normal values in relation to age. The use of this parameter in patients is shown to accurately reflect defects and changes in renal P handling. We believe it to be the preferred parameter because it represents a directly measured physiologic function applicable to all age-groups.

Hereditary hypophosphatemic rickets with hypercalciuria: report of a new kindred.

We report a new kindred of hereditary hypophosphatemic rickets with hypercalciuria. The symptomatic child and several relatives had increased renal phosphate clearance leading to hypophosphatemia, hyperabsorptive hypercalciuria, low PTH and increased 1,25-(OH)2D serum level. However, association with vitamin D deficiency and normal urinary excretion of cyclic AMP might suggest another tubular defect in phosphate transport.

Maffucci's syndrome--the result of neural abnormalities? Evidence of mitogenic neurotransmitters present in enchondromas and soft tissue hemangiomas.

BACKGROUND: Maffucci's syndrome (MS) is distinguished by the enigmatic association of benign cartilaginous bone tumors and soft tissue hemangiomas. METHODS: This study was conducted to define the distribution of nerves and neuropeptides around these tumors. Results were measured by quantitative image analysis of immunohistochemical staining. Four types of tissues were compared: connective tissues around normal muscles, solitary hemangiomas, MS hemangiomas, and MS enchondromas (the last two from a single patient). RESULTS: The number of nerves was found to be quadrupled in both types of hemangiomas as compared to normal connective tissue. A unique feature of MS tissues is the presence of an increased number of nerve fibers not only in the lesions but also in histologically normal margins of resection surrounding the lesions. Furthermore, hemangiomas of both types were found to contain a significantly higher number of calcitonin gene-related peptide-, substance P-, and methionine enkephalin-positive fibers than did normal muscle or its related fibroconnective tissue. These neuropeptides are mitogens, and their presence stimulates the growth of the abnormal blood vessels. Enchondroma fragments from an MS patient contained numerous methionine enkephalin-positive nerves. This neuropeptide is known to act as a growth factor in cartilage proliferation. CONCLUSIONS: A neural abnormality of the neuropeptidergic nervous system seems to relate to the abnormal tumors seen in MS.