Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 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

A 29-year-old male who had a past history of mild ECG abnormality of arrhythmia at the age of 14 years, was referred to our hospital because of elevated serum creatine kinase (CK) level. He had never been aware of muscular weakness nor cardiac symptoms. Neurological examination revealed normal muscle strength of all extremities except marked back muscle weakness. He had normal intelligence. On laboratory examination, serum AST, ALT, LDH, aldolase, CK and myoglobin levels were elevated. Both lactate and pyruvate levels were normally responded after an ischemic exercises test. Acid maltase activity was normal in white blood cells. A muscle biopsy obtained from rectus femoris muscle revealed vacuolar myopathy with mildly increased PAS positive material. On electron microscopy, there were autophagic vacuoles scavenging glycogen particles and cytoplasmic debris, and sarcolemmal indentation, compatible with the findings of lysosomal glycogen storage disease with normal acid maltase. This patient had unusual clinical features of absent mental retardation and no apparent cardiomyopathy. Accordingly, mental retardation is probably not necessary to see later onset of cardiac muscle involvement.
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PMID:[Lysosomal glycogen storage disease with normal acid maltase (Danon) without apparent cardiomyopathy and mental retardation]. 1088 38

Salla disease (SD) and infantile sialic acid storage disease (ISSD) are recessively inherited, neuro-degenerative disorders caused by mutations in the SLC17A5 gene. The gene product, sialin, is a lysosomal membrane protein which transports free sialic acid across the membrane. Although the function of sialin is basically known, the details of biosynthesis and intracellular trafficking as well as functional consequences of disease mutations in the SLC17A5 gene are not characterized. Here we studied for the first time the expression, localization, and targeting of the wild-type sialin as well as two mutant polypeptides; one mimicking the Finnish founder mutation, R39C (Salla(FIN)), and the other a deletion (del268-272) found in ISSD patients using in vitro expression of the corresponding cDNA constructs. The wild-type sialin was targeted to lysosomes whereas a significant fraction of the Salla(FIN) polypeptides and the majority of the ISSD polypeptides remained in the Golgi compartment. Further, using a temperature block of intracellular transport, we observed that the rate of the trafficking of the mutant polypeptides to lysosomes is significantly slower than that of their wild-type counterpart. These findings are in line with the phenotypic differences between SD and ISSD, the former presenting mental retardation with long life span in contrast to the latter being an early fatal disorder.
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PMID:Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin. 1517 96

Chanarin Dorfman syndrome is a multisystem, very rare, autosomal recessive lipid storage disorder, characterized by the accumulation of lipid vacuoles in neutrophils, and was first described by Dorfman in 1974. Due to a mutation in the ABHD5 gene of the short arm of chromosome 3, lipid is stored in the granulocytes at various sites in the human body, such as the muscle, liver, eye, ear, central nervous system, and bone marrow. Clinically, the disease is presented with ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation. A 38-year-old male patient was referred to our Internal Medicine Clinic for consultation with laboratory findings as follows: high aspartate aminotransferase (AST; 203 U/L), alanine aminotransferase (ALT; 151 U/L), gamma-glutamyl transferase (GGT; 167 U/L), creatine kinase (CK; 1127 U/L) levels and low platelet levels (108000). After ultrasonography and gastroscopy, the patient was diagnosed with liver cirrhosis. Bilateral mixed-type hearing loss on audial tests and bilateral punctuate keratopathy, ectropion, and cataract in the left eye on ophthalmological tests were found. For the definitive diagnosis of Chanarin Dorfman syndrome, peripheral blood was examined, which revealed lipid accumulation in the neutrophils (Jordan's anomaly). We emphasize that if a patient has unusual findings, such as ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation, the possibility of Chanarin Dorfman syndrome should be considered.
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PMID:Chanarin-Dorfman syndrome. 3045 58