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)

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.
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PMID:Polyamine Homeostasis in Snyder-Robinson Syndrome. 3054 65

Neurodevelopmental symptoms were previously believed to be a complication of celiac disease (CD) and rarely seen as presenting symptoms. One case has been reported so far where motor regression was the presenting symptom. We present a 16-month-old girl with postprandial vomiting and regression of motor skills. Examination revealed abdominal distension, hypotonia, and decreased motor movements in lower extremities. Celiac serology showed elevated tissue transglutaminase (tTG) immunoglobulin A (IgA) levels. Esophagogastroduodenoscopy with biopsies confirmed CD. Gluten-free diet led to the improvement of neurological and gastrointestinal complaints. We recommend keeping CD as one of the differentials in children with neurodevelopmental symptoms.
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PMID:Celiac Disease in a 16-Month-Old Child Presenting as Motor Regression. 3173 22