Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient was a right-handed boy. Pregnancy and delivery were normal. There were no neonatal complications. His development was normal until the age of 6 years and 10 months when he suddenly fell into coma. He was admitted to a hospital, where he was diagnosed as having encephalopathy of unknown cause. It was found that he did not respond to verbal stimuli after recovery from coma. He was referred to our hospital for detailed examination of hearing at the age of 7 years, and received neuroradiological and audiological examinations including X-ray CT, positron-CT, behavioral audiometry, auditory evoked response audiometry as well as other hearing and speech tests. Pure tone audiometry showed that auditory thresholds for pure tones ranging from 125 to 8,000 Hz were normal, while speech audiometry demonstrated that he was unable to discriminate test words. However, he accurately recognized environmental sounds and noises as well as sounds produced by musical instruments. The decreased uptake of 11C-glucose at the left temporal lobe was demonstrated by positron CT, although no abnormality was showed by X-ray CT. WISC-R showed he had normal intelligence. ITPA demonstrated that the psycholinguistic ability via visual channel remained intact, whereas auditory memory and auditory closure were markedly impaired. The boy had no difficulties in reading, naming and writing. Speech therapy was started as soon as diagnosis of word deafness was made. Until 6 months after onset, he never understood and repeated what was said to him.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Recovery process of auditory perceptual disorders in a child with word deafness]. 620 Jan 28

Human ITPase (encoded by the ITPA gene) is a protective enzyme which acts to exclude noncanonical (deoxy)nucleoside triphosphates ((d)NTPs) such as (deoxy)inosine 5'-triphosphate ((d)ITP), from (d)NTP pools. Until the last few years, the importance of ITPase in human health and disease has been enigmatic. In 2009, an article was published demonstrating that ITPase deficiency in mice is lethal. All homozygous null offspring died before weaning as a result of cardiomyopathy due to a defect in the maintenance of quality ATP pools. More recently, a whole exome sequencing project revealed that very rare, severe human ITPA mutation results in early infantile encephalopathy and death. It has been estimated that nearly one third of the human population has an ITPA status which is associated with decreased ITPase activity. ITPA status has been linked to altered outcomes for patients undergoing thiopurine or ribavirin therapy. Thiopurine therapy can be toxic for patients with ITPA polymorphism, however, ITPA polymorphism is associated with improved outcomes for patients undergoing ribavirin treatment. ITPA polymorphism has also been linked to early-onset tuberculosis susceptibility. These data suggest a spectrum of ITPA-related disease exists in human populations. Potentially, ITPA status may affect a large number of patient outcomes, suggesting that modulation of ITPase activity is an important emerging avenue for reducing the number of negative outcomes for ITPA-related disease. Recent biochemical studies have aimed to provide rationale for clinical observations, better understand substrate selectivity and provide a platform for modulation of ITPase activity.
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PMID:A disease spectrum for ITPA variation: advances in biochemical and clinical research. 2777 Aug 5

ITPA related epileptic encephalopathy (epileptic encephalopathy, early infantile, 35) is a rare inborn error of metabolism. All reported individuals with this condition, including the present case manifest global developmental delay, seizures, progressive postnatal microcephaly, hypotonia, thin corpus callosum, cerebral atrophy, delayed myelination and white matter changes in posterior limb of internal capsule. Cataract and dilated cardiomyopathy are other characteristic findings. Currently, a single publication describes this condition in four families. Three truncating and two missense variants in ITPA have been identified in these families. We hereby report another family with ITPA related disorder and review the genotype and phenotype of the reported subjects.
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PMID:Identification of a novel homozygous variant confirms ITPA as a developmental and epileptic encephalopathy gene. 3081 1

Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated "mutation negative" probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase). Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy. Severe ITPase-deficiency has been previously reported with infantile epileptic encephalopathy (MIM 616647). ITPase acts to prevent incorporation of inosine bases (rI/dI) into RNA and DNA. In Itpa-null cells dI was undetectable in genomic DNA. dI could be identified at a low level in mtDNA without detectable mitochondrial genome instability, mtDNA depletion or biochemical dysfunction of the mitochondria. rI accumulation was detectable in proband-derived lymphoblastoid RNA. In Itpa-null mouse embryos rI was detectable in the brain and kidney with the highest level seen in the embryonic heart (rI at 1 in 385 bases). Transcriptome and proteome analysis in mutant cells revealed no major differences with controls. The rate of transcription and the total amount of cellular RNA also appeared normal. rI accumulation in RNA-and by implication rI production-correlates with the severity of organ dysfunction in ITPase deficiency but the basis of the cellulopathy remains cryptic. While we cannot exclude cumulative minor effects, there are no major anomalies in the production, processing, stability and/or translation of mRNA.
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PMID:ITPase deficiency causes a Martsolf-like syndrome with a lethal infantile dilated cardiomyopathy. 3085 65