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)

Enzyme replacement therapy for a severely affected 6-month-old girl with hypophosphatasia was attempted by repeated intravenous infusions of alkaline phosphatase-rich plasma, obtained by plasmapheresis, from two men with Paget bone disease. Circulating Paget AP activity was found to have a half-life (two days) similar to that reported in adults, which did not change during a five-week period of six AP infusions. Normalization of the patient's serum AP activity was followed by better control of her hypercalcemia and hypercalciuria. Sequential radiographic studies revealed arrest of worsening rickets with slight remineralization of metaphyses, although urinary excretion of the AP substrates phosphoethanolamine and inorganic pyrophosphate was unaltered by therapy. Our findings suggest that the infantile form of hypophosphatasia results from defective production of AP rather than from accelerated destruction of circulating enzyme, and that hydrolysis of AP substrates like PEA and PPi occurs primarily in tissue rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.
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PMID:Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. 710 57

Pyridoxine-responsive seizures (PRS) and the role of pyridoxine (PN, vitamin B(6)) in hypophosphatasia (HPP) are incompletely understood. Typically, PRS and HPP are rare, independent, metabolic disorders. In PRS, seizures resist standard anticonvulsants apart from PN, yet have a good prognosis. In HPP, inactivation of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP) impairs skeletal mineralization and causes rickets in infants that can be fatal. Here, we report a 7-month-old girl, newly diagnosed with infantile HPP, who presented as a neonate with PRS but without bony abnormalities. Analysis of biogenic amines in cerebrospinal fluid (CSF) suggested brain pyridoxal 5'-phosphate (PLP) deficiency, although PLP in CSF was not decreased. She had normal cognitive milestones but failure to thrive and rickets. Nearly undetectable serum ALP activity, elevated plasma PLP and urinary phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi) levels, hypercalcemia, hypercalciuria and nephrocalcinosis were consistent with infantile HPP. Only prednisolone reduced serum calcium levels. Despite improved growth and weight gain, she developed rib fractures and died from respiratory failure at age 9 months. Sequence analysis of the TNSALP gene revealed novel missense mutations in exon 7 (c.677T>C, p.M226T) and exon 10 (c.1112C>T, p.T371I). Our patient demonstrated that PRS in neonates may not necessarily be "idiopathic"; instead, such seizures can be caused by severe HPP that becomes clinically apparent later in infancy. The pathophysiology of PRS in HPP differs from the three other genetic defects known to cause PRS, but all may lead to brain PLP deficiency reducing seizure thresholds. All reported HPP patients with neonatal seizures died within 18 months of birth, suggesting that PRS is an indicator of HPP severity and lethal prognosis. We recommend that assessment of any neonate with PRS should include measurement of serum ALP activity.
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PMID:Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. 1739 61