Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylosuccinate lyase (ASL) deficiency is a defect in purine de novo synthesis pathway. The disease has variable clinical presentation involving psychomotor retardation, seizures, hypotonia, and autism. The presence of succinyladenosine and succinylaminoimidazole carboxamide riboside (SAICA riboside) in body fluids characterizes the biochemical phenotype. All cases of ASL deficiency described to date have been diagnosed in Europe. Using a high-resolution thin-layer chromatography (TLC) technique combining screening for ASL deficiency and disorders of saccharide metabolism, we found the first case of this disease in the US. The patient presented with delayed motor development and profound hypotonia. The family history and routine laboratory tests were negative. Screening for metabolic disorders detected the presence of succinyladenosine and SAICA riboside in urine. The activity of ASL in the patient's skin fibroblasts was 43% of controls (patient, mean = 1.20 nmol/min/mg of protein, s = 0.21, n = 3; controls, mean = 2.78 nmol/min/mig of protein, s = 0.61, n = 7). In a 15-month-old girl with profound hypotonia, we established the diagnosis of ASL deficiency by demonstrating succinyladenosine and SAICA riboside in urine and decreased residual activity of ASL in skin fibroblasts.
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PMID:First U.S. case of adenylosuccinate lyase deficiency with severe hypotonia. 916 20

Adenylosuccinate lyase deficiency is an autosomal-recessive disorder of the purine de novo synthesis pathway, diagnosed up to now in approximately 40 patients. The clinical presentation is characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features. Neonatal seizures and a severe infantile epileptic encephalopathy are often the first manifestations of this disorder. The existence of genetic heterogeneity for the adenylosuccinate lyase defect could account for variability of the clinical presentation. Deficiency of purine nucleotides, impairment of energy metabolism, and toxic effects are potential mechanisms of cerebral damage. Laboratory investigations show the presence in urine and cerebrospinal fluid of succinylpurines, which are normally undetectable. Currently, no effective treatment is available for adenylosuccinate lyase deficiency. A search for this disorder should be included in the screening program of children with unexplained neonatal seizures or severe infantile epileptic encephalopathy.
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PMID:Neurologic aspects of adenylosuccinate lyase deficiency. 1139 13

A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X).
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PMID:Adenylosuccinate lyase deficiency--first British case. 1557 Dec 35

Adenylosuccinate lyase (ADSL) deficiency is a rare disease of de novo purine synthesis. The main symptoms are psychomotor retardation, epilepsy, autistic features, occasionally associated with muscular hypotonia. Diagnosis is made by detection of abnormal purine metabolites (succinyladenosine - S-Ado and succinylaminoimidazole carboxamide riboside - SAICAr) in body fluids. The severity of the clinical features correlates with low S-Ado/SAICAr ratio. We report clinical, biochemical and brain MRI findings of a female infant with severe early epilepsy and hypotonia, who died at the age of 10 weeks.
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PMID:Adenylosuccinate lyase deficiency: the first identified polish patient. 1748 88

Adenylosuccinate lyase (ADSL) catalyzes two steps in purine nucleotide metabolism-the 8th step in the de novo pathway: conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR), and conversion of adenylosuccinate (S-AMP) to adenylate (AMP) in the purine nucleotide cycle. To date, over 50 patients have been reported suffering from ADSL deficiency. We report all seven so far diagnosed Polish patients with this defect. Most of our patients shared intractable seizures and psychomotor retardation since the neonatal period and had biochemical evidence of severe (type I) deficiency. Two patients with type II suffered only from mild/moderate psychomotor retardation and showed a transientvisual contact disturbance. One patient had a fatal neonatal form of ADSL deficiency with lack of spontaneous movement, respiratory failure, severe encephalopathy and intractable seizures. Analysis of the ADSL gene showed that four apparently unrelated patients carried a R426H mutation (two homozygous and two compound heterozygous). With the exception of the latter mutation, a Y114H mutation that had been reported previously, and a novel mutation T242I, all other mutations (including D268H and three novel S23R, D215H and I351T mutations) were found only in single families in single alleles. A search for this disorder should be included in the screening program of all infants with unexplained neonatal seizures, severe infantile epileptic encephalopathy, developmental delay, hypotonia, and/or autistic features.
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PMID:Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency. 1852 58

Deficiency of adenylosuccinate lyase (ADSL) (OMIM 103050) is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycle, diagnosed so far in approximately 50 patients. The clinical presentation is characterized by severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life. At present there is no treatment of proven clinical efficacy. Despite of the increasing number of ADSL-deficient patients reported, there are only a few communications of therapeutic considerations or efforts. Among them only two showed some beneficial effects in ADSL-deficient patients. D-ribose, a simple and relatively cheap therapy, has been associated with improvement of behaviour and progressive reduction of the seizure frequency in one 13-year-old patient with ADSL deficiency. In this study we have re-examined D-ribose treatment in four ADSL-deficient patients. Assessments consisted of biochemical markers and neurological outcome. The 12-month trial of D-ribose failed to show any clinical benefit in ADSL patients with both milder and severe phenotype. D-ribose administration was accompanied by neither reduction in seizure frequency nor growth enhancement. Additionally, patients with milder type II presented the first seizure after 4 and 8 months of the D-ribose treatment. Therefore, we could not confirm a positive effect of D-ribose as previously reported.
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PMID:D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect. 1864 8

Adenylosuccinate lyase (ADSL) deficiency is an autosomal recessive disorder caused by mutation in the ADSL gene. The disease was identified in 1984 by Jaeken and van der Berghe as the first inborn defect of purine biosynthesis. Affected children revealed encephalopathy with epilepsy and marked psychomotor retardation. A neurological examination showed hypotonia, followed sometimes after years by spasticity. The diagnosis is based on detection in the urine and CSF succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAr). We present brain MR examinations of seven patients with ADSL deficiency in the correlation with their clinical findings. In all cases lack of myelination or of delayed myelination of cerebral white matter was seen. Additionally cerebral and cerebellar atrophy was observed. Neuropathological findings revealed damage of all cellular elements of brain tissue and are cause of observed MR changes. Hypo/dysmyelination seemed to be secondary to damage of oligodendroglia and axons of damaged neuronal cells.
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PMID:Severe encephalopathy with brain atrophy and hypomyelination due to adenylosuccinate lyase deficiency--MRI, clinical, biochemical and neuropathological findings of Polish patients. 2005 83

Adenylosuccinate lyase (ADSL) deficiency is an inherited metabolic disorder affecting predominantly the central nervous system. The disease is characterized by the accumulation of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in tissue and body fluids. Three children presented with muscular hypotonia, psychomotor delay, behavioral abnormalities, and white matter changes on brain MRI. Two of them were affected by seizures. Screening for inborn errors of metabolism including in vitro high resolution proton MRS revealed an ADSL deficiency that was confirmed genetically in all cases. All patients were studied by in vivo proton MRS. In vitro high resolution proton MRS of patient cerebrospinal fluid showed singlet resonances at 8.27 and 8.29 ppm that correspond to accumulated S-Ado. In vivo proton MRS measurements also revealed a prominent signal at 8.3 ppm in gray and white matter brain regions of all patients. The resonance was undetectable in healthy human brain. In vivo proton MRS provides a conclusive finding in ADSL deficiency and represents a reliable noninvasive diagnostic tool for this neurometabolic disorder.
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PMID:In vivo proton MR spectroscopy findings specific for adenylosuccinate lyase deficiency. 2017 47

Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease.
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PMID:Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency. 2305 21

Adenylosuccinate lyase deficiency is a rare genetic disorder with few reported cases in the United States. Magnetic resonance imaging findings in the brain include hypomyelination and low generalized parenchymal volume. Presented here is a case in a 3-month-old male who presented with hypotonia and seizures and was subsequently diagnosed with adenylosuccinate lyase deficiency. Given the rarity of this diagnosis, findings demonstrated in this case may prompt ordering physicians to broaden their approach to genetic testing in the setting of hypomyelination. Comparison is also made to more common hypomyelinating leukodystrophies.
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PMID:MRI findings of hypomyelination in adenylosuccinate lyase deficiency. 3051 Jun 7


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