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)

Alternating hemiplegia in childhood (Verret, 1971) is a disorder presenting with frequent episodes of alternating hemiplegia from early infancy. We report a patient with this disorder, along with a pathophysiological study and a discussion about the available therapies for this disorder. The patient, an 11-year-old boy, visited our hospital with episodes of alternating hemiplegia from early infancy. His family history showed that many members suffered from migraine. He was born with asphyxia. Mental and motor developmental delays were seen from early infancy. The hemiplegic episodes with ipsilateral facial palsy had occurred frequently from early infancy. The episodes were frequently induced by emotional stress. The duration of hemiplegia varied from 10 minutes to 3 days. From the age of 11 years, he had begun to have migrainous attacks with or without hemiplegic episodes. Neurological examination revealed slight muscle hypotonia, choreoathetosis and dystonic movements induced by locomotion, positive Myerson sign, increased deep tendon reflexes and Babinski reflex. CAG, VAG and CAT revealed normal findings. EEG revealed diffuse generalized slowing during hemiplegic episodes. Measurement of regional cerebral blood flow (CBF) by 133Xe inhalation method revealed a slight decrease of bilateral CBF during a quadriplegic episode. Positron emission tomography using C15O2 revealed a slight decrease of CBF at the insula, putamen and claustrum of the left side during a right sided episode. Increased excretion of urinary 5-HIAA was seen during one episode. From our clinical and laboratory findings, we think this disorder may be a special type of migraine. Therapeutic trials of diazepam and flunarizine were both effective, but the initial effectiveness was decreased after 5 months.
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PMID:[A patient with alternating hemiplegia in childhood]. 273 28

Aromatic l-aminoacid decarboxylase (AADC) deficiency is a neurotransmitter defect leading to a combined deficiency of catecholamines and serotonin. Patients are usually detected in infancy due to developmental delay, hypotonia, and extrapyramidal movements. Diagnosis is based on an abnormal neurotransmitter metabolite profile in CSF and reduced AADC activity in plasma. An elevation of vanillactic acid (VLA) has been described as the only abnormality detected in organic acid analysis (OA) of urine. We report a patient who presented in the neonatal period with lethargy, hypotonia, metabolic acidosis, and hypoglycemia. Blood ammonia, lactic acid, and acylcarnitines were normal, but OA of a urine sample showed a small increase of VLA, raising the suspicion of AADC deficiency. The patient was lost to follow-up until the age of 8 months, when he presented with dystonia, abnormal movements, oculogyric crises, and hypothermia. Repeat OA showed not only increased levels of VLA, but also increased vanilpyruvic acid (VPA), N-acetyl-vanilalanine (AVA) and N-acetyl-tyrosine (NAT). Neurotransmitter analysis in CSF showed increased vanilalanine (1200 nmol/L, ref<100) with decreased levels of 5-hydroxy-indoleacetic acid (5-HIAA, < 5 nmol/L; ref 152-462), homovanillic acid (HVA, 83 nmol/L; ref 302-845), and methoxy-hydroxy-phenyl-glycol (<5 nmol/L; ref 51-112). AADC activity in plasma was nearly undetectable. In the urine, low excretion of vanilmandelic acid (<0.3 micromol/mmol creat; ref 0.3-20) and 5-HIAA (0.9 micromol/mmol creat; ref 4-18), was found, but HVA was normal and dopamine even elevated. This contradictory phenomenon of hyperdopaminuria has been described earlier in AADC deficient patients. We postulate that VPA and AVA could originate from vanilalanine (through a transaminase and an acetylase respectively), while NAT could originate from tyrosine through an AA acetylase. This report expands the clinical presentation of AADC deficiency and adds new markers of the disease for OA analysis, improving detection of AADC deficient patients in general metabolic screening procedures.
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PMID:Aromatic l-aminoacid decarboxylase deficiency: unusual neonatal presentation and additional findings in organic acid analysis. 1628 91

Sepiapterin reductase (SR) catalyses the last step in the tetrahydrobiopterin biosynthesis pathway; it converts 6-pyruvoyl-tetrahydropterin (6-PTP) to BH(4) in an NADPH-dependent reaction. SR deficiency is a very rare autosomal recessive disorder with normal phenylalanine (Phe) concentration in blood and diagnostic abnormalities are detected in CSF. We present a 16-month-old girl with SR deficiency. From the newborn period she presented with an adaptation regulatory disorder. At the age of 3 months, abnormal eye movements with dystonic signs and at 4.5 months psychomotor retardation were noticed. Since that time axial hypotonia with limb spasticity (or rather delayed reflex development), gastro-oesophageal reflux and fatigue at the end of the day has been observed. Brain MRI was normal; EEG was without epileptiform discharges. Analysis of biogenic amine metabolites in CSF at the age of 16 months showed very low HVA and 5-HIAA concentrations. Analysis of CSF pterins revealed strongly elevated dihydrobiopterin (BH(2)), slightly elevated neopterin and elevated sepiapterin levels. Plasma and CSF amino acids concentrations were normal. A phenylalanine loading test showed increased Phe after 1 h, 2 h and 4 h and very high Phe/Tyr ratios. SR deficiency was confirmed in fibroblasts and a novel homozygous g.1330C>G (p.N127K) SPR mutation was identified. On L-dopa and then additionally 5-hydroxytryptophan, the girl showed slow but remarkable progress in motor and intellectual ability. Now, at the age of 3 years, she is able to sit; expressive speech is delayed (to 1 1/2 years), passive speech is well developed. Her visual-motor skills, eye-hand coordination and social development correspond to the age of 2 1/2 years.
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PMID:Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. 1913 Feb 91

Disruption of monoamines metabolism leads to diverse manifestations, including developmental, movement and respiratory dysfunctions. We aimed to correlate clinical phenotypes of 55 children with neurodevelopmental disorders with dopamine (HVA) and serotonin (5-HIIA) metabolites in CSF. Decreased level of at least one metabolite was documented in 49.1% patients. Both metabolites were significantly lower in progressive disorder and extrapyramidal syndrome (p<0.05). HVA was significantly lower in hypokinetic and regulatory disorders (p<0.05). In univariate analysis, only progressive course, extrapyramidal syndrome and dystonia were significantly associated with decreased 5-HIAA. In multivariate regression only progressive course remained significant (p=0.005). Progressive disease, extrapyramidal syndrome, dystonia, tremor and rigidity were positively associated with low HVA. In multivariate analysis only: progressive course and rigidity remained significant. Progressive/rigid phenotype carries a high risk of monoamines deficiency, strongly implying need for their analysis. Psychomotor delay with epilepsy and hypotonia is rarely linked to low monoamines level. Irrespective of final diagnosis, different clinical presentations may be associated with impaired monoamines turnover.
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PMID:Phenotypic features of children with neurodevelopmental diseases in relation to biogenic amines. 2551 85