Neonatal dopa-responsive extrapyramidal syndrome in twins with recessive GTPCH deficiency

Nardocci, Nardo; Zorzi, Giovanna; Blau, Nenad; Álvarez, Emilio; Sesta, Michela; Angelini, Lucia; Pannacci, Marilou; Invernizzi, Federica; Garavaglia, Barbara

doi:10.1212/01.wnl.0000044049.99690.ad

Cited by 41 publications

(35 citation statements)

References 10 publications

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“…54 Autosomal recessive GTP-CH-I deficiency Autosomal recessive GTP-CH-I deficiency is usually more severe than the autosomal dominant disease, and has a more complex neurological presentation with an earlier age of onset. [55][56][57][58] The condition is rare, and a family history is unusual. [55][56][57][58][59] Clinical presentations include truncal hypotonia, neonatal-onset rigidity, tremor, dystonia, spasticity, and oculogyric episodes.…”

Section: Introductionmentioning

confidence: 99%

Dopa-responsive dystonia—clinical and genetic heterogeneity

2015

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Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

Dopa-responsive dystonia—clinical and genetic heterogeneity

2015

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“…So far six different autosomal recessive mutations associated with GCH1 deficiency were reported Ichinose et al, 1995;Furukawa et al, 1998;Hirano and Ueno, 1999;Hwu et al, 1999;Nardocci et al, 2003;www.bh4.org/BH4_Start.asp). Here, we add another recessive case with DRD patient with two novel mutations.…”

Section: Discussionmentioning

confidence: 99%

“…When both GCH1 was deficient (OMIM 605407), the patients usually presents with neonatal hyperphenylalaninemia and encephalopathy with severe mental retardation, seizures, abnormal muscle tone and movements Ichinose et al, 1995;Furukawa et al, 1998;Nardocci et al, 2003). However, a patient with homozygous recessive mutation of GCH1 was reported to have mild symptoms of typical DRD study (Hwu et al, 1999), suggesting more complex interplay of GCH1 muta- Figure 2.…”

Section: Introductionmentioning

confidence: 99%

Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele

et al. 2008

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Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.

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“…8,9 (2) Late infantile or juvenile onset forms. First reported by Segawa as 'hereditary progressive dystonia with marked diurnal fluctuation', and later designated as Dopa-responsive dystonia, this condition is now-adays considered a clinical syndrome.…”

Section: Phenotypesmentioning

confidence: 99%

Movement disorders in children: Recent advances in management

Fernández-Álvarez

2009

Indian J Pediatr

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In recent years there has been a growing interest towards pediatric movement disorders (PMD). The data derived from the synthesis of clinical observation, neuroimaging, biochemical and, molecular genetics studies have allowed for the identification of a significant number of pediatric diseases featuring movement disorders. The purpose of this review is to outline an approach to the advances in management of dystonia, neurotransmitter disorders, tics, and paroxysmal dyskinetic syndromes starting in children younger than 18 yr of age.

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Neonatal dopa-responsive extrapyramidal syndrome in twins with recessive GTPCH deficiency

Cited by 41 publications

References 10 publications

Dopa-responsive dystonia—clinical and genetic heterogeneity

Dopa-responsive dystonia—clinical and genetic heterogeneity

Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele

Movement disorders in children: Recent advances in management

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