Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Dutch child with psychomotor retardation, impaired speech, ataxia, sialic acid storage and vacuolized skin fibroblasts and lymphocytes was diagnosed as having free sialic acid storage disease. Slight corneal opacities, pale optic disks at the fundus oculi and vertebral abnormalities, not earlier reported in Salla disease, were peculiar to this case. Free sialic acid was about tenfold increased in urine and cultured fibroblasts, without changes in the glycoconjugate-bound sialic acid pool. A subsequent pregnancy of the patient's mother was monitored by assay of sialic acid in chorionic villi and amniotic fluid. An unaffected foetus was predicted. Sialic acid was also assayed in peripheral blood total leucocytes, and in mononuclear and polymorphonuclear (PMN) leucocyte subpopulations. Each of these leucocyte fractions from the patient showed 10- to 30-fold increase in sialic acid content. The PMN subpopulation provided the most restricted range of control values and showed slightly increased values for the patient's parents. These results suggest that the assay of sialic acid in PMN might be useful for the identification of heterozygotes in sialic acid storage disease. Studies on a larger number of obligate heterozygotes are needed to confirm this observation.
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PMID:Salla disease variant in a Dutch patient. Potential value of polymorphonuclear leucocytes for heterozygote detection. 150 79

Increased amounts of free sialic acid were found in body fluids, leukocytes, cultured fibroblasts, and liver tissue of a four-year-old boy with mental retardation, ataxia, and clinical and radiologic findings of a mild mucopolysaccharidosis. A diagnosis of Salla disease was made though in contrast to earlier reports, recurrent upper respiratory infections and hepatosplenomegaly were present already in infancy, and skeletal abnormalities of dysostosis multiplex were found in early childhood. Free sialic acid in the urine was identified as N-acetylneuraminic acid by 1H-NMR spectroscopy. Sialidase activities were normal. Increased amounts of bound sialic acid were found in liver and cultured fibroblasts and were attributed to an intracellular inhibition of sialyloligosaccharide-degrading neuraminidase by excessive amounts of free neuraminic acid. The molecular basis of N-acetylneuraminic acid storage disease is unknown but may be related to a defective transport mechanism preventing neuraminic acid from leaving the lysosomal compartment.
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PMID:N-Acetylneuraminic acid storage disease. 404 64

The first case of infantile sialic acid storage disease in Czech Republic is presented in a four-and-half year-old girl. The clinical phenotype consisted of moderate hepatosplenomegaly and skin hypopigmentation, early psychomotoric and developmental arrest, associated with truncal ataxia and lower extremities spasticity, extinguished acoustic and visual perception (optic atrophy without macular alteration) and remarkable automutilation phenomena. The appearance was normosomatic and there were minimal dysostotic changes. Skin and liver biopsy displayed moderate amount of lucent storage lysosomes in epithelial, mesenchymal, and neural elements. Alder-Reily granules were found in the bone marrow and peripheral blood cells. The urinary excretion of mucopolysaccharides and oligosaccharides was not increased. The autopsy showed heterogenous neuronal and glial brain storage (lucent lysosomes, lipopigment, membranous cytoplasmic bodies), severe hypomyelination and severe storage in the splenic sinus endothelium. Diagnosis was made by proving thirteen fold increase of free sialic acid in the fibroblast culture. It is pointed out that in the case of a mucopolysaccharidosis-like storage disease unexplainable by a hydrolytic enzyme deficiency, it is the enzyme product storage which must be suspected. At present, the only candidate is the sialic acid storage disease.
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PMID:Infantile sialic acid storage disease (ISSD). Report on first case in Czech Republic with biopsy and autopsy findings. 799 7

N-acetylneuraminic acid (sialic acid) storage disease is a rare autosomal recessive lysosomal disorder. Clinically two major forms exist, an infantile type with severe progression leading to early death, and a milder form (Salla disease) with a protracted course. Intermediate forms may also exist. Diagnosis rests on the determination of an excessive excretion of sialic acid in urine and concomitant storage in fibroblasts, the severe forms exhibiting the highest excretion and storage. We present clinical, morphological, and biochemical data on three non-Finnish patients with sialic acid storage disease. Patient 1 was a preterm infant with neonatal ascites, coarse face, hepatosplenomegaly, pale skin, and wispy hair. Vacuolated lymphocytes were abundant in a peripheral blood smear and he excreted large amounts of free sialic acid. High levels of free sialic acid were also found in cultured skin fibroblasts. He died at age 6 months from progressive respiratory insufficiency. Patient 2 was an 11-month-old Egyptian girl with coarse face, frequent upper respiratory tract infections, hepatosplenomegaly, and severe psycho-motor retardation. Sialic acid excretion was elevated, likewise the storage in fibroblasts. Histological investigations documented vacuolar storage in a skin biopsy and in iliac crest tissue. Patient 3 was a 16-year-old girl with slightly coarse face, severe generalized muscular hypotonia, ataxia, and kyphoscoliosis originally diagnosed as having post-partum asphyxia. She suffered progressive motor function loss and had dysarthria. Urinary sialic acid was elevated and a skin biopsy demonstrated vacuolization. The clinical variability of sialic acid storage disease is exemplified by these three cases. Simple urinary screening for free sialic acid facilitates the diagnosis. The degree of urinary excretion may indeed correlate with clinical presentation and progression.
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PMID:The spectrum of free neuraminic acid storage disease in childhood: clinical, morphological and biochemical observations in three non-Finnish patients. 872 11

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15-bp deletion in exon 6 on one of the alleles. This mutation is the same described in French-Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum).
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PMID:An Italian severe Salla disease variant associated with a SLC17A5 mutation earlier described in infantile sialic acid storage disease. 1212 52

Four members of an extended consanguineous Bedouin family presented with different phenotypic variants of an autosomal recessive lysosomal free sialic acid storage disease. One affected individual had congenital ascites followed by rapid clinical deterioration and death, a presentation concordant with the clinical course of infantile free sialic acid storage disorder. His three first cousins had a more slowly progressive neurodegenerative disease, in line with the clinical phenotype of the milder form (Salla type) of this lysosomal disorder. Diagnosis of free sialic acid storage disease was based on clinical findings, histology, and biochemical assays of sialic acid. Molecular studies showed that all four affected individuals were homozygous for the same novel 983G > A mutation in exon 8 of the SLC17A5 gene, replacing glycine with glutamic acid at position 328 of the sialin protein. This family demonstrates the significant phenotypic variability of the disease in affected members of a single inbred kindred with precisely the same mutation, suggesting a role for modifier genes or environmental factors. It also highlights the need to consider this rare disorder in the differential diagnosis of congenital ascites and of unexplained psychomotor retardation, ataxia, and hypomyelination in infancy.
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PMID:A novel mutation in the SLC17A5 gene causing both severe and mild phenotypes of free sialic acid storage disease in one inbred Bedouin kindred. 1517 96