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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

A neuropathological study was performed on two patients with Salla disease, one male and one female, from different families. They both died at the age of 41 years. Both patients showed increased excretion of free sialic acid in the urine, psychomotor retardation starting in the 1st year of life, ataxia and spasticity. Several family members of both families were affected with the same disease indicating the hereditary character of the disorder. The neuropathological investigation revealed strikingly similar changes in the two cases. Macroscopically the cerebral white matter was severely reduced. Histologically marked loss of axons and myelin sheaths was accompanied by pronounced astrocytic proliferation. The remaining axons frequently showed ovoid swellings surrounded by a myelin sheath. The reduction of the number of myelin sheaths seemed proportional to the numerical reduction of axons. Many cortical nerve cells displayed in relation to age an abnormal amount of lipofuscin. Neurofibrillary tangles were observed in nerve cells of the neo-cortex, nucleus basalis of Meynert and locus ceruleus. Cerebellum showed moderate loss of Purkinje cells. In the spinal cord axonal degeneration was observed in both ascending and descending tracts.
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PMID:Neuropathology of Salla disease. 328 34

Salla disease is an autosomal recessive lysosomal storage disease relatively common in the Finnish population. The main manifestations of more than 70 patients detected to date are severe psychomotor retardation and ataxia of early onset. Intracellular free N-acetylneuraminic acid (sialic acid) is increased 10-20-fold and localized in the lysosomes. Four pregnancies at risk were monitored by quantitation of free and total sialic acid in amniocytes and supernatant amniotic fluid by high-performance liquid chromatography. In 3 children results were normal. Free sialic acid content of the amniocytes from one affected child was 2.6 nmol/mg protein, which was approximately 5 times higher than that of the 3 unaffected children (0.3 to 0.8) and 14 control samples (0.3 to 0.9). The ratio of free/total sialic acid of the amniocytes also clearly distinguished the affected pregnancy (13.8%) from the unaffected (2.3-4.8%) and control individuals (1.8-5.3%). This represents the first successful prenatal identification of a patient with Salla disease and indicates that both free sialic acid and free/total sialic acid ratio should be monitored in pregnancies at risk for the disease.
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PMID:Prenatal detection of Salla disease based upon increased free sialic acid in amniocytes. 342 17

In a 5-year-old boy, an early onset psychomotor retardation with non-progressive ataxia and without dysmorphic features, associated with lysosomal storage disease found on ultrastructural examination of the conjunctiva, led to the diagnosis of Salla disease. This was supported by a tenfold excretion of urinary free sialic acid, without abnormal oligosacchariduria or anomaly in lysosomal enzymes. This boy is a native of Southern France. Screening of urinary sialic acid has to be introduced in aetiological investigations of patients with apparently non-progressive psychomotor retardation associated with ataxia or dystonic movements.
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PMID:Salla disease in one non-Finnish patient. 377 5

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

Salla disease is a lysosomal storage disorder associated with increased urinary excretion of free sialic acid. The main clinical features in 34 patients were severe psychomotor retardation of early onset, ataxia, athetosis, rigidity, spasticity, and impaired speech. Growth retardation, thick calvarium, and exotropia were present in about half the patients. The amplitude of EEG decreased progressively with increasing age. Life span appears to be normal; the age range of the patients was 3 to 63 years. Genealogic studies suggest an autosomal mode of inheritance. A thin-layer method is described for the detection of increased urinary free sialic acid excretion. The basic defect is so far unknown.
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PMID:Salla disease: a new lysosomal storage disorder with disturbed sialic acid metabolism. 668 60

Salla disease (SD) is a recessively inherited lysosomal storage disorder particularly common in the Finnish population. Patients with SD are normal at birth, but develop psychomotor delay and ataxia during the first year of life. Phenotypic variation of SD is wide, ranging from severely disabled children to mentally retarded adults capable of living under sheltered conditions. In the present study four unusually severely affected patients were investigated by detailed clinical examination, magnetic resonance imaging (MRI) and analysis of the excretion of free sialic acid in urine. MRI study, reported here for the first time, revealed a similarly defective myelination pattern in seven patients. The myelination process seemed to cessate at the level of an infant of a few months of age. Genetic linkage study of the families of the severely affected patients suggested linkage to the recently discovered SD locus on the long arm of chromosome 6. Locus heterogeneity therefore is an unlikely explanation of the phenotypic variation in SD.
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PMID:Phenotypic variation and magnetic resonance imaging (MRI) in Salla disease, a free sialic acid storage disorder. 788 32

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

Salla disease represents the slowly progressive adult form of the sialic acid storage diseases, a group of autosomal-recessive neurodegenerative disorders in which psychomotor development, ataxia, axial hypotonia, and spasticity in the lower limbs occur. No skeletal dysostosis or organomegaly is present, and life expectancy is normal. Short stature can also be observed. Progressive cerebral and cerebellar atrophy associated with dysmyelination and corpus callosum hypoplasia have been shown by magnetic resonance imaging studies. We report the first patient with Salla disease in whom combined growth hormone and gonadotropin deficiencies, hypothalamic pituitary in origin, have been demonstrated by neuroendocrine studies. We believe that the multiple neuroendocrine disorder may be the consequence of the abnormalities of common neuronal pathways regulating growth hormone and gonadotropin synthesis or secretion related to the brain storage of free sialic acid and/or to the neurodegenerative process occurring in Salla disease. Therefore, a complete endocrinologic evaluation of these patients is both warranted and useful.
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PMID:Multiple neuroendocrine disorder in Salla disease. 1166 56

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


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