Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis.

Pelizaeus-Merzbacher disease (PMD) is X-linked hypomyelinating leukodystrophy caused by mutations of the PLP1 gene, which codes the proteolipid protein 1. The result of mutations is abnormal myelination - hypomyelination and dysmyelination of cerebral white matter, and in some form of the disease hypomyelinating peripheral neuropathy. DNA samples from 68 patients suspected of PMD due to the clinical course and hypomyelination at magnetic resonance imaging (MRI) were analyzed. Medical history and detailed clinical course of PMD patients were also analyzed. Different mutations of the PLP1 gene were detected in 14 boys from 11 families (~20%). Amongst the molecularly confirmed patients, 13 presented classical PMD forms but clinical phenotypes varied in the severity even amongst siblings. One patient presented a severe connatal form. One mother, obligate carrier, presented complicated SPG2 (spastic paraparesis). There was no phenotype-genotype correlation in our material. In many cases PMD was suspected with a delay of many years, sometimes only after birth of another affected child in the family. Pelizaeus-Merzbacher disease was most frequently misdiagnosed as cerebral palsy.

Magnetic resonance spectroscopy and molecular studies in ornithine transcarbamylase deficiency novel mutation c.802A>G in exon 8 (p.Met268Val).

Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited de-fect in ureagenesis, resulting in hyperammonaemia type II. The OTC gene, localised on chromosome X, has been mapp-ed to band Xp21.1, proximate to the Duchenne muscular dystrophy (DMD) gene. More than 350 different mutations, including missense, nonsense, splice-site changes, small de-letions or insertions and gross deletions, have been describ-ed so far. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Most mutations in the OTC gene are 'private' and are distributed throughout the gene with a paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. They have familial origin or occur de novo. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remainder probably occur within the introns or in regulatory domains. The authors present a 4-year-old boy with the unreported missense mutation c.802A>G. The nucleotide transition leads to amino acid substitution Met to Val at codon 268 of the OTC protein.

Do children with Adams-Oliver syndrome require endocrine follow-up? New information on the phenotype and management.

Adams-Oliver syndrome (AOS) is a rare genetic condition in which the main diagnostic criteria are terminal transverse limb defects and aplasia cutis congenita. Within the spectra of the clinical phenotype of AOS, anthropometric abnormalities have also been reported. We present growth pattern along with hormonal assays in three patients with AOS, one being treated with growth hormone (GH). In Patient 1 (a boy, age 1.9 years), with delayed psychomotor development, epilepsy, deficits of body mass and height, cryptorchidism, low insulin-like growth factor (IGF-1) levels were found and magnetic resonance imaging (MRI) revealed hypoplasia of midline structures of the central nervous system (CNS). In Patient 2 (a girl, age 3.6 years) no significant abnormalities in development, body mass, height or neuroimaging were found. In Patient 3 (a girl, age 8.2 years), with delayed psychomotor development and short stature, low IGF-1 levels and partial GH deficiency were found; MRI revealed small pituitary and polymicrogyria. The girl started GH treatment, improving height velocity and gross coordination. Based on these observations, it seems that intensity of auxologic and hormonal deficits in children with AOS is associated with CNS lesions. Hence, there are indications for neuroimaging and interdisciplinary follow-up of psychomotor development, growth and puberty in this subset of patients with AOS.

[Progressive encephalopathies in children]. / Encefalopatie postepujace u dzieci.

The Authors describe progressive encephalopathies in children hospitalized at the Department of Child Neurology Silesian Medical School from 1980 to 2000. They present ethiology, clinical symptoms and diagnostic protocol based on literature data and their own experience.

Agenesis of corpus callosum: clinical description and etiology.

In 135 children (aged 3 months to 15 years) with structural defects of the central nervous system found on magnetic resonance imaging, agenesis of the corpus callosum was evident in 7. The etiology of agenesis of the corpus callosum has been established in four children: partial trisomy of chromosome 13, partial duplication of the long arm of chromosome 10, Aicardi's syndrome, and intracranial bleeding during the fetal period as a result of injury. Agenesis of the corpus callosum coexisted with a Dandy-Walker malformation in one other patient, which suggests a genetic etiology. In spite of these variable etiologies, dysmorphic features were identified in all seven patients, as was psychomotor retardation. Epileptic seizures had occurred in six patients, and all manifested abnormalities on neurologic examination.

[Cerebral tumors as a cause of refractory epilepsy in children]. / Procesy rozrostowe wewnatrzczaszkowe jako przyczyna padaczki lekoopornej u dzieci.

Cerebral tumours are a cause of seizures in less than 1-2% of children epilepsy. Seizure symptoms usually precede the diagnosis by several years and are often the only symptoms of an ongoing process. The symptomatology of the seizures often correlates with localization of a neoplastic lesion. The authors present six children aged 3 to 18 in whom epileptic seizures not susceptible to treatment were caused by cerebral tumours. The duration of epilepsy until the determining of the aetiology was various--from half a year to 13 years. In each of our six patients focal epilepsy occurred with simple or complex seizures with secondary generalization. It was only one patient in whom the tomography of the head turned out to be sufficient enough to establish the diagnosis of a brain tumour; in the other ones MR was necessary. The final diagnosis in four of the children was supported by histopathologic examination carried out during a neurosurgical procedure, whereas in one of them--by means of biopsy of the brain.

Variability of localization and intensity of damage of the white matter of the brain and cerebellum in genetically conditioned diseases.

The investigations were based on 3 cases with Leigh, 5 cases with Krabbe's, 4 cases of Alpers, 2 cases with Sandhoff, 1 case with Alexander's disease and 1 case with metachromatic leukodystrophy. In 1 case included into the study we have diagnosed nonketotic hyperglycinemia II. All the diseases under examination are recognized as genetically conditioned or are supposed to be of genetic origin. Damage of the white matter in a more delineated form in certain regions was found in Leigh disease. The changes demonstrated a variable degree of intensity from demyelination to necrosis. More extensive lesions of white matter in gyri and semivoal centrum were found in diseases with simultaneously damaged gray matter e.g. in Alpers and Sandhoff disease. The most extensive changes of diffuse demyelination were found in Krabbe's and Alexander's disease. In these diseases demyelination was accompanied with specific morphological structures e.g. globoidal cells (Krabbe's disease) and Rosenthal fibers (Alexander's disease). The peculiar type of demyelination was characteristic for nonketotic hyperglycinemia of type II. It was expressed by demyelination with vacuolization.

[Lyme disease in children]. / Borelioza u dzieci.

In the recent years the number of diagnosed cases of Lyme Disease has tended to increase. This is due to the possibility of serological examinations. Between 1992-95 at the Neurological Department of 2nd Chair of Pediatrics Silesian Medical Academy in Katowice 7 children with Lyme Disease were hospitalized. The authors analysed the clinical course, important laboratory and serological data and treatment effects.

[Silver-Russel Syndrome in aa 13-month old girl]. / Zespól Silvera-Russela u 13-miesiecznej dziewczynki.

The authors present a case of 13-month girl with Silver-Russel syndrome, which is an example of intrauterine growth retardation. The etiology of the disorder remains unknown, although many data suggest the embryopathy of the early gestational period. The main clinical features are: low height, decreased birth weight and normal gestational age. Body asymmetry and craniofacial dysmorphy.

Ultrastructure of peripheral blood lymphocytes in some degenerative central nervous system disease.

The ultrastructure of peripheral blood lymphocytes of 30 children with degenerative central nervous system diseases was analyzed. The affected children were divided into four groups. Lysosomal storage were characterized by the storage of membrane-bound inclusions in peripheral lymphocytes. Ceroidlipofuscinosis was manifested by the presence of curvilinear bodies. The appearance of abnormal mitochondria was found in mitochondrial encephalopathies. The tubuloreticular structures seen in lymphocytes of some unclassified cases suggested viral factors that acted in prenatal life. All findings confirm the role of peripheral lymphocytes analysis in the diagnosis of degenerative central nervous system diseases.

[Congenital toxoplasmosis in a 6-week-old infant]. / Toksoplazmoza wrodzona u 6-tygodniowego niemowlecia.

A case of congenital toxoplasmosis was observed in an infant aged 6 weeks with fatal outcome. Histological changes produced by Toxoplasma gondii in the brain are described.

Fibrinoidal leucodystrophy (Alexander's disease) at 13 months girl. A case report.

The case of Alexander's fibrinoidal leucodystrophy that was presented below is an exemplar of extremely rare degenerative disease of the CNS. On the grounds of the clinical course of the disease it seems that our case can be reckoned as an early childhood form of Alexander's disease. An interesting difference that pays attention is the marked hydrocephalus. In the most cases of Alexander's disease the volume of ventricular system is normal however most of authors expresses that it sometimes can be slightly and insignificantly enlarged.

[Leigh disease in a 3-year-old girl]. / Choroba Leigh'a u trzyletniej dziewczynki.

A case of Leigh disease in a 3-year-old girl is reported. The child had regression of the psychomotor development, muscular hypotonia, weak tendinous reflexes, opsoclonus, tremor of the whole body, hypertrichosis, autonomic system disturbances. Laboratory investigations demonstrated raised serum lactic acid level. Postmortem histological examination of the brain confirmed the diagnosis of Leigh disease established before death.