Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysinuric protein intolerance is an autosomal recessive metabolic disorder caused by defective transport of the cationic amino acids lysine, arginine and ornithine in the epithelial cells of the basolateral membrane in the small intestine and renal tubules. Mutations in the solute carrier family 7, member 7, SLC7A7, gene cause this multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. In the present study, genomic structure of SLC7A7 in six Turkish patients with lysinuric protein intolerance was examined in order to detect disease causing mutations by denaturing high pressure liquid chromatography and direct sequencing. Four novel mutations were identified in SLC7A7: c.223insGTC, p.Val74_Ile75insVal; c.283insTGG, p.Glu94_Thr95insTrp; c.344_347delTTGC, p.Leu115LeufsX53; and c.1099insT, p.Ile367TyrfsX16. Clinical and biochemical findings were evaluated together with these molecular analyses.
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PMID:Molecular and clinical evaluation of Turkish patients with lysinuric protein intolerance. 2354 76

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is the result of impaired glucose transport into the brain. The "classic" GLUT1DS patient presents with infantile seizures (resistant to traditional seizure medications), developmental delay, acquired microcephaly, hypotonia, spasticity, and a complex movement disorder consisting of ataxia and dystonia. However, over the years, other clinical manifestations have been described, such as paroxysmal exertion-induced dystonia with or without seizures, choreoathetosis, alternating hemiplegia, and other paroxysmal events, such as intermittent ataxia, dystonia, and migraine. At the current state of the art in understanding of GLUT1DS, classifying the disease phenotype as "classical" or "non-classical" seems to be of limited clinical utility. It seems more appropriate to think in terms of a broad clinical spectrum in which we can observe intellectual impairment, acquired microcephaly, epilepsy, and movement disorders characterized by different clinical manifestations and degrees of severity. Lumbar puncture, a simple investigation, should be considered the first diagnostic step that, moreover, is feasible worldwide. Thereafter, mutational analysis of the solute carrier family 2 (facilitated glucose transporter) member 1 (SLC2A1) gene should be performed in patients with highly suggestive clinical findings and low cerebrospinal fluid glucose (<50mg/dl or ratio <0.60). Early diagnosis is critical because it allows prompt initiation of treatment with a ketogenic diet (KD). Childhood is the critical period for treatment of GLUT1DS: early diagnosis is crucial for an effective etiological therapy. KD treatment can be useful in adulthood too. Compliance has been found to be much better in GLUT1DS than in the other conditions for which KD treatment is indicated.
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PMID:GLUT1 deficiency syndrome 2013: current state of the art. 2389 Aug 38

Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay on the brain magnetic resonance imaging (MRI) of affected subjects. We report a patient with Allan-Herndon-Dudley syndrome characterized by developmental delay, hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R). The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley syndrome. The follow-up examinations showed that the progression of the myelination was not accompanied by a clinical improvement. Our paper suggests that SLC16A2 mutations should be investigated in patients with myelination delay even when the thyroid function is not conclusively altered.
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PMID:Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene. 2538 Jun 3

Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.
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PMID:Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8. 2663 78

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) was first described by De Vivo in 1991, and the classic clinical manifestations include infantile epilepsy, developmental delay, and acquired microcephaly. A neurological complex disorder including elements of hypotonia, spasticity, ataxia, and dystonia can frequently be present. GLUT1-DS is an inborn error of metabolism caused by impaired glucose transport through blood-brain barrier in the majority of patients because of mutation of solute carrier family 2 (facilitated glucose transporter) member 1 gene (SLC2A1), encoding the transporter protein. We report a 6-year-old girl with GLUT1-DS, which is caused by a novel heterozygous variant c.109dupC of the SLC2A1 gene. The dominating clinical features were ataxia, epilepsy started at 4 years, acquired microcephaly, and mild intellectual disability. Treatment with ketogenic diet showed clinical improvement with the reduction of ataxia and seizure control in a 10-month follow-up period.
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PMID:Glucose Transporter Type 1 Deficiency Syndrome: Developmental Delay and Early-Onset Ataxia in a Novel Mutation of the SLC2A1 Gene. 3093 99