Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 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.
 ...
PMID:A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. 1058 Oct 36

The French Indian Ocean island Mayotte was hit by an outbreak of chikungunya in January 2005. The purpose of this retrospective study is to report data recorded over a five-month period (February - June 2006) in the pediatric-neonatal department of the Hospital Center in Mayotte. The study cohort includes a total of 50 children in whom chikungunya was confirmed by molecular tools. Mean age was 9.3 years and the male-to-female sex ratio was 1:5. The main symptoms were intense pain (88%), high fever (82%), and skin rash (80%) that was less common in children under 2 years of age. Neurological complications were observed in 46% of patients including hypotonia (22%) that occurred mainly in newborns, meningitis syndrome (18%) and convulsions (16%) that occurred mainly in children over 2 years of age. Infectious complications included pneumonia (4%), pyelonephritis (2%), and possible nosocomial septicemia due to Pseudomonas (6%). The main hematological abnormalities were lymphopenia (27%) and thrombopenia (16%). Serum CRP values were moderately high (mean, 25 mg/l). Elevated AST (24%) and ALT (10%) values were observed. High CSF protein levels were noted in 30% of cases. A total of 25 children required hospitalization for more than 10 days. There were two deaths in newborns infected before the seventh day of life. The main risk factors for hospitalization longer than 10 days were premature birth and age at the time of chikungunya infection.
 ...
PMID:[Confirmed chikungunya in children in Mayotte. Description of 50 patients hospitalized from February to June 2006]. 1906 81

Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m(2) (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.
 ...
PMID:Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report. 2083 May 24