Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal recessive forms of infantile dystonia due to mutations in the tyrosine hydroxylase (TH) gene have been described recently. The main clinical manifestations are Segawa's disease, or infantile hypokinetic rigid Parkinsonism. Here, we report on a patient with hyperrigidity, psychomotor developmental delay, and dystonic posturing of the hands, symptoms that appeared after a viral infection at the age of 14 months. Low homovanillic acid/5-hydroxyindolacetic acid (HVA/5HIAA) ratio in cerebrospinal fluid suggested a TH deficiency. Molecular analysis revealed a novel (H246Y) and a known (D498G) compound heterozygote mutation in the TH gene. The patient showed a remarkable response to treatment with levodopa. The new mutation and the association of viral infections with the onset and worsening of symptoms are discussed.
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PMID:Levodopa-responsive infantile parkinsonism due to a novel mutation in the tyrosine hydroxylase gene and exacerbation by viral infections. 1574 53

Methylmalonic acidaemia (MMA) is a rare autosomal recessive inborn error of metabolism that typically presents in infancy with recurrent episodes of metabolic acidosis, developmental delay and failure to thrive. The disease course is complicated by the development of chronic tubulointerstitial nephritis progressing to end-stage renal disease in adolescence. We describe two adolescents with cobalamin-nonresponsive MMA (mut0) who developed polyuria, chronic tubulointerstitial nephritis, dystonia but normal synthetic liver function. Both patients received combined liver-kidney transplantation (CLKT), preceded by a single pretransplant haemodialysis for clearance of methylmalonic acid. Post CLKT there was 95-97% reduction in serum and urine methylmalonic acid, leading to significant liberalization of dietary protein intake and a consequent increase in body mass index, muscle strength and energy. In addition, renal function normalized and clinical neurological status stabilized. We propose that CLKT be considered as a therapeutic option early in the course of cobalamin-nonresponsive MMA. Progressive tubulointerstitial nephritis with disabling polyuria is a confounder in patient management even in the absence of end-stage renal disease. Successful CLKT restores methylmalonyl-CoA mutase enzyme levels in the liver and kidney, improves clearance of methylmalonic acid with resultant dietary protein liberalization, and offers excellent graft and patient outcomes with improvement in quality of life.
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PMID:Management of methylmalonic acidaemia by combined liver-kidney transplantation. 1590 54

Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening programs. We describe an 8-year-old girl with delay, seizures, and dystonia with mild hyperphenylalaninemia detected in late childhood. The diagnosis of 6-pyruvoyl-tetrahydrobiopterin synthase deficiency was made by analysis of pterins in urine, pterins and neurotransmitters in cerebrospinal fluid, and enzyme assay. The patient improved clinically taking oral tetrahydrobiopterin, levodopa/carbidopa, and 5-hydroxytryptophan. This treatable condition may not always be detected by routine population screening for hyperphenylalaninemia.
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PMID:6-pyruvoyl-tetrahydropterin synthase deficiency with mild hyperphenylalaninemia. 1598 17

Neurophysiologic abnormalities are frequently seen in organic acidemias, but knowledge of the specific changes in the different types of organic acidemias is lacking. We studied electroencephalogram (EEG), visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) in seven children with glutaric aciduria type I (GA1) to assess the neurophysiologic features in this rare inborn error of metabolism. Age at the time of the diagnosis ranged between 3 months and 36 months. Age at the time of neurophysiologic evaluation ranged between 11 months and 36 months. At the time of neurophysiologic evaluation, severe global developmental delay was seen in four patients, dystonia in four patients, motor delay in two patients, and axial hypotonia in two patients; macrocephaly, spasticity, moderate mental retardation and borderline intelligence were each seen in one patient. One patient had autistic features characterized by lack of language and social skills, poor eye contact and stereotypical behavior. Three of seven patients showed abnormal EEG findings. Two patients showed asymmetry with intermittent occipital delta slowing in one hemisphere. This finding probably indicates underlying cerebral dysfunction, and is not a specific feature. However, it suggests that these patients may develop abnormal EEG features during the course of the disease, and thus a baseline EEG may be useful for comparison over time. One patient showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and baclofen. We believe this finding was due to medication effect, and that what we observed was an exaggarated response to benzodiazepine. The clinical significance of this finding is unclear. VEP and BAER were available in four patients, and we found abnormalities in three of them. Neurophysiologic evaluation may be helpful in patients with GA1 as in other types of organic acidemias to help detect subtle changes that are not reflected by neurological examination or neuroimaging studies, and it may guide future treatment plans. Detailed neurophysiologic analysis in a large series of GA1 may yield further information regarding the extent of cerebral dysfunction.
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PMID:Neurophysiologic features in glutaric aciduria type I. 1605 56

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

Two siblings from a Hong Kong Chinese family are diagnosed to have heterozygous mutation in tyrosine hydroxylase gene-a novel mutation R169X and the common Dutch mutation R233H. Presented with developmental delay and dystonia before 6 months of age, both had hyperprolactinemia with persistent galactorrhea present in the elder brother since birth. Serum prolactin level is a good screening test for those suspected of underlying neurotransmitter diseases. To our knowledge, this is the first Chinese family diagnosed with such condition. Clinicians must be aware of this rare disease especially in those unexplained 'cerebral palsy' like children.
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PMID:Galactorrhea-a strong clinical clue towards the diagnosis of neurotransmitter disease. 1637 43

Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive neurodegenerative disorder of childhood. Thirteen patients with this syndrome seen over a period of 7 years were reviewed. Two distinct groups were identified. The early onset childhood group had uniform presentation with developmental delay, recurrent falls, gait abnormalities, cognitive deterioration and dystonia. This group was also characterised by familial incidence, retinal involvement and absence of behavioural problems. Late onset group, included patients with different presentations such as behavioural changes, optic atrophy and dystonia. Consanguinity was prominent in this study, being present in 61.5% patients. MRI (n=11) showed pallidal hyperintensity on T1-weighted images and hypointensity or 'eye of the tiger' sign on T2-weighted images. Two patients had acanthocytes in peripheral blood smear. This study emphasizes the phenotypic heterogeneity in HSS and as well brings out the common features shared by patients with early onset disease.
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PMID:Clinical heterogeneity in Hallervorden-Spatz syndrome: a clinicoradiological study in 13 patients from South India. 1650 38

The diagnosis of a 14-year-old girl with a new homoallelic mutation in the sepiapterin reductase (SR) gene is reported. Initially she presented at the age of 2 with hypotonia and mild cognitive developmental delay, and was diagnosed as having mild methylmalonic aciduria, which was recently identified as methylmalonylCoA racemase deficiency, a new defect in valine-isoleucine metabolism. After a 12-year progression of her neurologic condition, which had made her wheelchair-bound at the age of 6, dystonia with diurnal variation had become apparent. At the age of 14 this finding led to rapid diagnosis of SR deficiency. The diagnostic approach with CSF neurotransmitter and pterins analysis and combined phenylalanine/BH(4) loading test, and finally measurement of sepiapterin in CSF is illustrative for the diagnosis of SR deficiency. As in all other patients with this new defect, very low levels of homovanillic acid and 5-hydroxyindoleacetic acid and high levels of biopterin and sepiapterin in the CSF are the diagnostic hallmark. The girl improved dramatically on treatment with L-DOPA and 5-hydroxytryptophan. The initial diagnosis of methylmalonic aciduria may afterwards be considered to have not significantly contributed to her clinical condition and only has led to a long delay of the clinically relevant diagnosis of SR deficiency. Although the clinical condition of this recently recognized autosomal recessive defect in pterin metabolism is complex and many symptoms can occur in variable severity and time of onset, dystonia with diurnal variation is a characteristic finding, as shown in nearly all patients described so far. The rapid and favourable response on treatment with L-DOPA warrants the classification of SR deficiency as another autosomal recessive type of DOPA-responsive dystonia (DRD). This classification is important to improve the awareness of clinicians that more than one metabolic defect can underlie the phenotype of a DOPA-responsive dystonic disorder and that dystonia should always trigger a rapid diagnosis of the underlying neurotransmitter synthesis defect, in view of the excellent treatability of a DRD.
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PMID:Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia. 1665 Jul 84

A 12 year old boy with gradually worsening global developmental delay was diagnosed and managed as quadriplegic cerebral palsy since child-hood. Subsequent evaluation revealed marked dystonia over spasticity leading to suspicion of Segawa syndrome. Dramatic improvement in clinical condition followed after therapy with low dose L-Dopa.
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PMID:Dopa-responsive dystonia (Segawa syndrome). 1689 85

To date, there are few reports of paroxysmal exercise-induced dystonia associated with familial epilepsy. We describe a family with 4 affected members spanning 3 generations, suggestive of autosomal-dominant inheritance, who exhibited typical exercise-induced dystonia, different types of epilepsy (absence and primary generalized seizures), developmental delay, and migraine in variable combinations. Linkage of the disease to loci on chromosome 2 (paroxysmal nonkinesigenic dyskinesia) and chromosome 16 (paroxysmal kinesigenic choreoathetosis, infantile convulsions with choreoathetosis) was excluded, suggesting an as yet unidentified underlying genetic basis.
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PMID:New family with paroxysmal exercise-induced dystonia and epilepsy. 1729 Apr 64


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