1,721,185 research outputs found
Leucodistrofia metacromatica: un caso di pubertà precoce
No full textLeucodistrofia metacromatica: un caso di pubertà precoce
Nardecchia F 1
, Poratti E 1
, Dimiccoli P 1
, Di Maggio C 1
, Commone A 1
, Pucci C 1
, Leuzzi V 1
1DAI Neurosc e Sal Ment, Univ Sapienza, Roma
INTRODUZIONE/BACKGROUND: La leucodistrofia metacromatica è una malattia lisosomiale,
autosomica recessiva, caratterizzata
dall'accumulo di solfatidi a livello della mielina del sistema nervoso e, in minor quantità, nei tessuti
a funzione escretoria, tra cui reni, fegato e cistifellea. E’ stato descritto, inoltre, coinvolgimento di
tipo deficitario dell’ipofisi anteriore, surreni, testicoli, ovaie ed endometrio.
METODI / PAZIENTI:Il caso presentato è una bambina di 7,6 anni con esordio tipico intorno ai 2,6
anni, caratterizzato
da rapida regressione psicomotoria e ipotono. La RMN dell’encefalo mostarva diffusa e marcata
iperintensità di segnale della
sostanza bianca biemisferica sovratentoriale, con coinvolgimento del corpo calloso. Il dosaggio dell
dell’attività dell’arilsulfatasi A rivelava una riduzione del 91% e l’indagine genetica una eterozigosi
composta per [p.Tyr201Cys] e [p.Leu428Pro] nel gene ARSA. A 6 mesi dalla diagnosi comparsa di
episodi critici polimorfi. Intorno ai 4 anni osservato telarca
bilaterale isolato e incremento della lanuggine corporea, con successiva comparsa di pubarca.
RISULTATI:Il GnRH test evidenziava un’attivazione dell’asse ipotalamo-ipofisi- gonadi,
definendo un quadro di
pubertà precoce centrale. L’ecografia pelvica mostrava alcuni follicoli bilaterali con diametro di 3
mm. L’Rx polso evidenziava un’età ossea avanzata rispetto a quella cronologica, con uno scarto
superiore ad un anno. La progressione del quadro neurologico ha determinato un quadro di
tetraparesi spastico-distonica, assenza di linguaggio e residuo ed incostante contatto di sguardo.
Assume terapia antiepilettica con crisi plurisettimanali e trattamento ormonale con analoghi del
GnRH.
DISCUSSIONE:A differenza del riscontro di ipofunzionamento dell’asse ipotalamo-ipofisi- gonadi
descritto nelle
leucodistrofie e consensuale al processo degenerativo, si segnala in questo caso l’iperattivazione
dell’asse, finora non descritta in letteratura
The Spectrum of Early Movement Disorders in Congenital Defects of Biogenic Amine Metabolism
No full textThis article analyzes the pattern of movement disorders in children with primary defects of biogenic amine metabolism emerging during the first 3 year of life. A PubMed search was performed using the keywords monoamine neurotransmitter disorders, congenital defects of biogenic amine metabolism, early onset movement disorders, autosomal dominant guanosine-triphosphate-cyclohydrolase deficiency, autosomal recessive guanosine-tryphosphate-cyclohydrolase deficiency, 6-pyruvoyl-tethrahydropterin synthase deficiency, sepiapterin reductase deficiency, dihydropteridine reductase deficiency, tyrosine hydroxilase deficiency, aromatic l-amino acid decarboxylase deficiency, dopamine transporter deficiency, and vesicular monoamine transporter 2. A personal series of 27 patients affected by these disorders was presented and discussed. Primary defects of biogenic amine metabolism result in a spectrum of movement disorders associated with derangement of postural reaction and global development delay. Movement disorders virtually represent the presentation symptoms in most of these diseases. The prominent early clinical patterns of movement disorders are akinesia (with rigidity or hypotonia) and hyperkinesia (dystonia, myoclonic jerks, and tremor). While some diseases present with a rather stereotyped clinical pattern (i.e.; Aromatic l-amino acid decarboxylase, sepiapterin reductase, and Dopamine transporter deficiencies), others (i.e.; Guanosine-triphosphate-cyclohydrolase, 6-pyruvoyl tetrahydropterin synthase, dihydropteridine reductase, and tyrosine hydroxylase deficiencies) may present with more pleomorphic features. As a general rule, earlier the onset of the disease is, more severe and generalized is the derangement of motor functions. Inherited disorders of monoamine neurotransmitter metabolism include the few idiopathic movement disorders with the possibility of etiological treatments. For these reasons, they should always be considered in the diagnostic work-up of children with early onset movement disorders
Treatable Inherited Movement Disorders in Children: Spotlight on Clinical and Biochemical Features
Full text linkBackground: About 80% of monogenic metabolic diseases causing movement disorders (MDs) emerges during the first 2 decades of life, and a number of these conditions offers the opportunity of a disease-modifying treatment. The implementation of enlarged neonatal screening programs and the impressive rapid increase of the identification of new conditions are enhancing our potential to recognize and treat several diseases causing MDs, changing their outcome and phenotypic spectrum. Methods and Findings: A literature review of monogenic disorders causing MDs amenable to treatment was conducted focusing on early clinical signs and diagnostic biomarkers. A classification in 3 broad categories based on the therapeutic approach has been proposed. Some disorders result in irreversible neurotoxic lesions that can only be prevented if treated in a presymptomatic stage, and others present with a progressive neurological impairment that a timely diagnosis and treatment may reverse or improve. Some MDs are the result of the failure of intracellular energy supply or altered glucose transport. The treatment in these conditions includes vitamins or a metabolic shift from a carbohydrate to a fatty acid catabolism, respectively. Finally, a group of highly treatable MDs are the result of defects of neurotransmitter metabolism. In these disorders, the supplementation of precursors or mimetics of neurotransmitters can deeply change the disease natural history. Conclusions: To prevent serious and irreversible neurological impairment, the diagnostic work-up of MDs in children should consider a number of clinical red flags and biomarkers denoting specifically treatable diseases
Deficit delle Funzioni esecutive nei bambini con fenilchetonuria:alcuni dati sperimentali
No full textArginine and glycine stimulate creatine synthesis in creatine transporter 1-deficient lymphoblasts
No full textCreatine transporter 1 (CT1) defect is an X-linked disease that causes severe neurological impairment. No treatment has been available for this condition so far. Because the transport of creatine (Cr) precursors Gly and Arg is not affected in this disorder, we tested the possible corrective effect of these two amino acids on Cr depletion in lymphoblasts lacking the transporter. Substrates enriched with Arg or Arg plus Gly increased the concentration of intracellular Cr in affected cells as well as in control cells. The greatest effect was obtained with 10 and 15 mM Arg and 10 mM Arg plus Gly. These results encourage an in vivo trial with Cr precursors in CT1 defect
Genetic neonatal-onset epilepsies and developmental/epileptic encephalopathies with movement disorders: A systematic review
Full text linkDespite expanding next generation sequencing technologies and increasing clinical in-terest into complex neurologic phenotypes associating epilepsies and developmental/epileptic encephalopathies (DE/EE) with movement disorders (MD), these monogenic conditions have been less extensively investigated in the neonatal period compared to infancy. We reviewed the medical literature in the study period 2000–2020 to report on monogenic conditions characterized by neonatal onset epilepsy and/or DE/EE and development of an MD, and described their electroclinical, genetic and neuroimaging spectra. In accordance with a PRISMA statement, we created a data collection sheet and a protocol specifying inclusion and exclusion criteria. A total of 28 different genes (from 49 papers) leading to neonatal-onset DE/EE with multiple seizure types, mainly featuring tonic and myoclonic, but also focal motor seizures and a hyperkinetic MD in 89% of conditions, with neonatal onset in 22%, were identified. Neonatal seizure semiology, or MD age of onset, were not always available. The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants. The outcome is characterized by high rates of associated neurodevelopmental disorders and microcephaly. Brain MRI findings are either normal or nonspecific in most conditions, but serial imaging can be necessary in order to detect progressive abnormalities. We found high genetic heterogeneity and low numbers of described patients. Neurological phenotypes are complex, reflecting the involvement of genes necessary for early brain development. Future studies should focus on accurate neonatal epileptic phenotyping, and detailed description of semiology and time-course, of the associated MD, especially for the rarest conditions
PRICKLE1-Related Disorders
Full text linkClinical characteristics: Individuals with biallelic PRICKLE1-related disorders typically present with progressive myoclonus epilepsy (PME) with ataxia characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, varying degrees of neurologic regression mainly presenting with ataxia, and mild cognitive impairment or normal cognition. Onset of symptoms is between ages five and ten years. Action myoclonus may affect the limbs or bulbar muscles, while spontaneous myoclonus may occasionally involve facial muscles. Dysarthria may also be an early feature of this condition. The main seizure types are myoclonic or tonic-clonic with frequent nocturnal occurrence.
Individuals with heterozygous PRICKLE1 pathogenic variants have presented with non-PME seizures (isolated myoclonic seizures, juvenile myoclonic epilepsy), myoclonic epilepsy, developmental delay, intellectual disability, autism spectrum disorder, and/or central nervous system malformations.
Diagnosis/testing: The diagnosis of a PRICKLE1-related disorder is established in a proband with suggestive findings and biallelic or heterozygous pathogenic variant(s) in PRICKLE1 identified by molecular genetic testing.
Management: Treatment of manifestations: Occupational therapy, psychomotricity/physical therapy, and speech therapy for ataxia and neurodevelopmental impairment; adaptive devices as needed to maintain or improve independence in mobility and feeding; anti-seizure medications as needed, such as valproic acid, clonazepam, zonisamide, and levetiracetam.
Surveillance: Neurologic examination every six months; developmental assessment and evaluation of school performance and emotional status every six to 12 months as needed based on age.
Agents/circumstances to avoid: Phenytoin, carbamezapine, oxycarbazpine, gabapentin, pregabalin, tiagabine, and vigabatrin may worsen myoclonic seizures.
Genetic counseling: PRICKLE1-related PME with ataxia is associated with biallelic homozygous or compound heterozygous PRICKLE1 pathogenic variants and inherited in an autosomal recessive manner. PRICKLE1-related phenotypes associated with a heterozygous PRICKLE1 pathogenic variant are inherited in an autosomal dominant manner.
Autosomal recessive inheritance. If both parents of a proband with PRICKLE1-related PME with ataxia are known to be heterozygous for a PRICKLE1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial PRICKLE1 pathogenic variants.
Autosomal dominant inheritance. An individual with an autosomal dominant PRICKLE1-related disorder may have the disorder as the result of a de novo pathogenic variant or a pathogenic variant inherited from a parent. Each child of an individual with a heterozygous PRICKLE1 pathogenic variant has a 50% chance of inheriting the pathogenic variant.
Once the PRICKLE1 pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for PRICKLE1-related disorders are possible
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