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- Namavar, Yasmin, et al.
(author)
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Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.
- 2011
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 134:Pt 1, s. 143-56
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Journal article (peer-reviewed)abstract
- Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P < 0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations.
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- Ohlsson, M., et al.
(author)
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Follow-up of nemaline myopathy in two patients with novel mutations in the skeletal muscle alpha-actin gene (ACTA1)
- 2004
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In: Neuromuscular Disorders. - : Institute of Information Science. - 0960-8966 .- 1873-2364. ; 14:8-9, s. 471-475
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Journal article (peer-reviewed)abstract
- Nemaline myopathy has been associated with mutations in five different genes, which all encode protein components of the sarcomeric thin filaments. We report follow-up studies in two children with mutations not previously described in skeletal muscle alpha-actin (ACTA1). Case 1 was a male patient who after birth suffered from pronounced muscle weakness and hypotonia. Muscle biopsy showed small fibers with numerous rods. He failed to achieve any motor milestones. At the age of 17 he required 24 h ventilator support. He could not lift his arms against gravity, but he could use his hands to control his electric wheelchair. The muscle biopsy showed marked replacement of muscle tissue by fat and connective tissue. Only few fibers showed nemaline rods. He had a de novo, heterozygous mutation, G268D in ACTA1. Case 2 was a female patient with feeding difficulties and mild hypotonia in the neonatal period. Muscle biopsy showed hypoplastic muscle fibers and numerous rods. At 11 years of age she walked and moved unhindered and could run fairly well. She had a de novo, heterozygous mutation, K373E, in ACTA1. These two patients illustrate the marked variability in the clinical features of nemaline myopathy in spite of similar muscle pathology in early childhood. The severe muscle atrophy with replacement of fat and connective tissue in case 1 demonstrates the progressive nature of nemaline myopathy in some cases. The described two mutations add to the previously reported mutations in ACTA1 associated with nemaline myopathy.
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- Bergström, T, et al.
(author)
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[Gene amplification in viral CNS infections. Rapid diagnostic identification of herpesviruses]. : Genamplifiering vid virala CNS-infektioner. Snabb diagnostik av herpesgruppens virus.
- 1995
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In: Lakartidningen. - 0023-7205. ; 92:5, s. 427-32
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Journal article (peer-reviewed)abstract
- DNA amplification with the polymerase chain reaction (PCR) technique was used as a diagnostic test on cerebrospinal fluid samples in cases where herpesvirus infection of the central nervous system (CNS) was suspected. During the period, 1992-93, 47 (8.9%) of 528 patients tested were positive for one or another of the following herpesviruses: herpes simplex virus type 1 (n = 16) or type 2 (n = 9), cytomegalovirus (n = 16), varicella-zoster virus (n = 4), or Epstein-Barr virus (n = 2). The study showed PCR to be a rapid and useful diagnostic method in clinical routine, enabling early antiviral intervention in several cases with an atypical clinical picture. Moreover, cytomegalovirus was found to be an important CNS pathogen in addition to herpes simplex virus, especially during childhood.
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- Darin, Niklas, 1964, et al.
(author)
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Clinical, serological and PCR evidence of cytomegalovirus infection in the central nervous system in infancy and childhood.
- 1994
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In: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 25:6, s. 316-22
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Journal article (peer-reviewed)abstract
- Over a 3-year-period (Dec. 1990-Nov. 1993) 12 children were found PCR-positive for CMV-DNA in CSF and brain biopsies. Three of the patients were immunologically compromised. During the same period CSF samples from 10 shunt-operated children and 143 virological routine CSF samples were PCR CMV negative. Clinical association with positive PCR-CMV reaction was considered likely in 6 patients: two boys developed prolonged fever and meningoencephalitis following neurosurgery, one infant girl had a course compatible with congenital inclusion disease, and three had prolonged fever following transplantation. Clinical association was deemed probable in 3 infant girls: one had neonatal infection, meningitis and intraventricular haemorrhage, one had neonatal encephalitis and failure to thrive, and one with neonatal seizures and encephalitis developed brain atrophy. Clinical association was judged possible in 3 patients: one infant girl with no signs of encephalitis developed brain atrophy, one had an Aicardi Type 1 syndrome and one 2 1/2-year-old boy had an acute encephalitis with insufficient serological support for CMV but was 12 months later PCR positive for CMV. We conclude that CMV may be an overlooked infectious agent of the CNS also in immunocompetent children. PCR aids in rapid diagnosis of CMV infection in the immunocompromised. CMV may occasionally be disclosed with PCR in other conditions as a probably non-relevant observation.
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- Kölker, Stefan, et al.
(author)
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Diagnosis and management of glutaric aciduria type I--revised recommendations.
- 2011
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In: Journal of inherited metabolic disease. - : Wiley. - 1573-2665 .- 0141-8955. ; 34:3, s. 677-94
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Journal article (peer-reviewed)abstract
- Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline.
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