Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes the clinical and biologic data and bone density measurements in 19 adults seen in a rheumatology department, with phosphate diabetes defined by low serum phosphate levels and decreased tubular reabsorption of phosphate in the absence of known etiology. There were 14 males and 5 females with a mean age at disease onset of 36.7 years (20-68 years) and at diagnosis of 43.9 years (24-70 years). Axial pain was present in 17 patients (90%), radicular pain in 13 patients (68%), pain at night in 14 patients (74%), fatigue in 7 patients (37%), myalgia in 6 patients (32%), fracture in 6 patients (32%), renal colic in 4 patients (21%) and depression 10 patients (53%). Mean serum phosphorus was 2.25 mg/dL (1.08-2.76); maximum tubular reabsorption of phosphate/glomerular filtration rate was 0.58 (0.4-0.76) (n > 0.77). Calcium/creatinine > 0.48 was seen in 9 patients (47%), indicating an associated hypercalciuria. Serum calcium, sodium, magnesium, creatinine, cortisol, T3, T4, thyroid-stimulating hormone (TSH), 25 and 1,25 OH2 vitamin D3 were normal. Glucose and amino acid were absent from urine. Bone mineral density at L2-L4 level (Z-score) was -2.13 (-0.9 to -4.25), and at the femoral neck was -1.34(-1.5 to -3.2). Bone biopsy in 5 patients showed osteoporosis with minor osteoid deposition.Idiopathic phosphorus diabetes (IPD) is a rheumatic disease with chronic axial pain at night, radiculitis-like symptoms, fatigue and depression. In half of the patients, IPD is associated with hypercalciuria. Bone mineral density at L2-L4 and femoral neck level is low. Bone biopsies show osteoporosis. Chronic pain, fatigue and depression resulting from IPD may be improved by treatment with oral calcitriol and phosphorus. There might be a delay in improvement of a few months, even if the blood phosphate level is normalized. A 3% increase in bone mineral density could be measured at 6-month intervals when blood phosphate was maintained. This disease is often misdiagnosed when the maximal reabsorption rate of phosphorus is not calculated.
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PMID:Adult onset idiopathic phosphate diabetes. 1907 33

Hypophosphatasia (HPP) is due to mutations of the tissue non-specific alkaline phosphatase (TNAP) gene expressed in the liver, kidney, and bone. TNAP substrates include inorganic pyrophosphate cleaved into inorganic phosphate (Pi) in bone, pyridoxal-5'-phosphate (PLP), the circulating form of vitamin B6, and phosphoethanolamine (PEA). As an autosomal recessive or dominant disease, HPP results in a range of clinical forms. Its hallmarks are low alkaline phosphatase (AP) and elevated PLP and PEA levels. Perinatal HPP may cause early death with respiratory insufficiency and hypomineralization resulting in deformed limbs and sometimes near-absence of bones and skull. Infantile HPP is diagnosed before 6 months of life. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency in the brain indicate poor prognosis. Craniosynostosis is frequent. Unlike in other forms of rickets, calcium and phosphorus are not decreased, resulting in hypercalciuria and nephrocalcinosis. Hypercalcemic crisis may occur. Failure to thrive and growth retardation are concerns. In infantile and adult forms of HPP, non-traumatic fractures may be the prominent manifestation, with otherwise unexplained chronic pain. Progressive myopathy has been described. Dental manifestations with early loss of teeth are usual in HPP and in a specific form, odontohypophosphatasia. HPP has been studied in knock-out mice models which mimic its severe form. Animal models have made a major contribution to the development of an original enzyme therapy for human infantile HPP, which is however essentially targeted at mineralized tissues. Better knowledge of its extraskeletal manifestations, including pain and neurological symptoms, is therefore required.
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PMID:Clinical Forms and Animal Models of Hypophosphatasia. 2621 4

Hypophosphatasia (HPP) is a rare inherited systemic metabolic disease caused by mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. TNSALP is expressed in the liver, kidney and bone, and its substrates include TNSALP inorganic pyrophosphate, pyridoxal-5'-phosphate (PLP)/vitamin B6 and phosphoethanolamine (PEA). Autosomal recessive and dominant forms of the disease result in a range of clinical entities. Major hallmarks are low alkaline phosphatase (ALP) and elevated PLP and PEA levels. Very severe infantile forms of HPP cause premature death as a result of respiratory insufficiency and also present with hypo-mineralisation leading to deformed limbs with, in some cases, the near-absence of bones and skull altogether. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency are indicative of a poor prognosis. Craniosynostosis is frequent. HPP leads to an unusual presentation of rickets with high levels of calcium and phosphorus, resulting in hypercalciuria, nephrocalcinosis and low ALP levels. Hypercalcaemic crisis, failure to thrive and growth retardation are concerns in infants. Fractures are common in both infantile and adult forms of the disease, concomitantly occurring with unexplained chronic pain and fatigue. Dental clinical presentations, which include the premature loss of teeth, are also commonly found in HPP and specifically manifest as odontohypophosphatasia. A novel enzyme therapy for human HPP, asfotase alfa, which is specifically targeted to mineralised tissues, has been developed in the past decades. While this treatment seems very promising, especially for infantile HPP, many questions regarding its long-term effects, the management of treatment, and any potential secondary adverse effects remain unresolved.
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PMID:Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy. 3215 59