Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder caused by virtually complete deficiency of activity of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8). Human HPRT is encoded by a single structural gene located on the long arm of the X-chromosome (Xq26). The classical LND phenotype occurs almost exclusively in males, manifested in excessive purine production and characteristic neurological manifestations, including compulsive self-mutilation, choreoathetosis, spasticity, and occasionally developmental delay. Heterozygous females are usually phenotypically normal, due to the random inactivation of the X chromosome (Lyonization mechanism). However, six females were reported to be affected with the full biochemical and clinical manifestations of LND. All these cases were heterozygous for an HPRT mutation. Absence of transcription of the normal HPRT allele was attributed in all of them to non-random inactivation of the X chromosome carrying the normal allele. Here we describe an additional LND female, who presented with acute renal failure at the age of two months, in whom absence of transcription of the two HPRT alleles occurred due to as yet undescribed mechanism in LND females: the transcription of one HPRT allele was blocked due to a de novo X chromosome-autosome translocation 46,XX,t(X:2)(q26:p25), with a breaking point encompassing the HPRT gene locus, whereas the transcription of the normal allele was inhibited due to non-random inactivation of the second X-chromosome. Cultured fibroblasts from this patient exhibited the biochemical alterations in purine nucleotide metabolism characteristic of male LND fibroblasts.
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PMID:Molecular, biochemical, and genetic characterization of a female patient with Lesch-Nyhan disease. 1634 67

A 9-year old male patient with a past medical history of congenital cytomegalovirus (CMV) infection and spastic quadriplegic cerebral palsy with an intrathecal baclofen pump was admitted to a tertiary care hospital with respiratory depression and unresponsiveness for approximately two days. He had a recent two-week hospital stay for respiratory failure due to pneumonia. After being prescribed antibiotics and being sent home, he had developed copious diarrhea. On readmission, he was found to be dehydrated and in acute renal failure. A physical exam revealed hypotonia throughout, in a patient who typically had spasticity with contractures. The Pediatric Rehabilitation Medicine service was consulted for possible baclofen toxicity. Some signs and symptoms of baclofen toxicity include respiratory depression, seizures, CNS depression, hypotonia, hypotension, absent deep tendon reflexes, lethargy, ataxia, and cardiac arrhythmias. His intrathecal baclofen (ITB) dose was reduced, and signs/symptoms of ITB overdose began to resolve. As renal function improved, spasticity returned, necessitating increase in ITB dosing toward the premorbid dose.
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PMID:Intrathecal baclofen toxicity in a patient with acute kidney injury. 3147 82