Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialic acid storage diseases (SASD, MIM 269920) are autosomal recessive neurodegenerative disorders that may present as a severe infantile form (ISSD) or a slowly progressive adult form, which is prevalent in Finland (Salla disease). The main symptoms are hypotonia, cerebellar ataxia and mental retardation; visceromegaly and coarse features are also present in infantile cases. Progressive cerebellar atrophy and dysmyelination have been documented by magnetic resonance imaging (ref. 4). Enlarged lysosomes are seen on electron microscopic studies and patients excrete large amounts of free sialic acid in urine. A H+/anionic sugar symporter mechanism for sialic acid and glucuronic acid is impaired in lysosomal membranes from Salla and ISSD patients. The locus for Salla disease was assigned to a region of approximately 200 kb on chromosome 6q14-q15 in a linkage study using Finnish families. Salla disease and ISSD were further shown to be allelic disorders. A physical map with P1 and PAC clones was constructed to cover the 200-kb area flanked by the loci D6S280 and D6S1622, providing the basis for precise physical positioning of the gene. Here we describe a new gene, SLC17A5 (also known as AST), encoding a protein (sialin) with a predicted transport function that belongs to a family of anion/cation symporters (ACS). We found a homozygous SLC17A5 mutation (R39C) in five Finnish patients with Salla disease and six different SLC17A5 mutations in six ISSD patients of different ethnic origins. Our observations suggest that mutations in SLC17A5 are the primary cause of lysosomal sialic acid storage diseases.
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PMID:A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. 1058 Oct 36

Mitochondrial functions are intimately associated with neurological symptoms. Various clinical and biological features are suggestive of energy depletion diseases, such as Leigh syndrome, Alpers syndrome, epilepsy (including myoclonic seizures and status epilepticus), stroke-like episodes, and acute cerebellar ataxia with high lactate peaks on magnetic resonance spectroscopy. Magnetic resonance imaging (MRI) discloses abnormalities in over 90% of the cases presenting with neurological symptoms. Basal ganglionic involvement, the most frequent imaging sign, can be isolated or combined with subtentorial atrophy of both the cerebellum and brainstem. MRS monovoxel proton spectroscopy is useful to reveal high lactate spikes if placed in the putamen and the cerebellar dentate nucleus. Lactate and pyruvate levels are required to exclude pyruvate dehydrogenase deficiency. However, lactate may be normal in the CSF. Clinical and biochemical investigations guide molecular studies, with two major heredities: mtDNA point mutations and autosomal recessive defects that program the majority of respiratory chain subunits. Muscle biopsy is the first test demonstrating the histochemical and ultrastructural alterations in mitochondria, even in diseases in which myopathy is not clinically prominent, and is also a good tissue for biochemical analysis, as the biopsy is not dangerous for the patient. Negative results in skeletal muscle do not exclude respiratory chain deficiency, and a liver biopsy may be necessary whatever the blood AST and ALT levels, to perform biochemical and molecular investigations. Only the identification of nuclear or mitochondrial mutation confirms the diagnosis.
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PMID:Respiratory chain deficiencies. 2362 86