Biomedical subjects

Hanna Mierzewska

Publications and source records attributed to Hanna Mierzewska.

10 recordsLinked to original sources

PubMed2006

Leukoencephalopathy with vanishing white matter due to homozygous EIF2B2 gene mutation. First Polish cases.

Leukoencephalopathy with vanishing white matter (VWM), also called childhood ataxia with central nervous system hypomyelination (CACH), is an autosomal recessive disease caused by mutations in any of the five genes encoding subunits of the eukaryotic translation initiation factor eIF2B. Neuropathological findings comprise a severe, cavitating orthochromatic leukodystrophy with only small amounts of myelin breakdown products, and predominantly involving the cerebral hemispheric white matter. Within the white matter abnormal oligodendroglial cells are present with abundant "foamy" cytoplasm. In some regions oligodendroglial cells are increased in numbers. We present three sisters, 18, 11 and 8 years old, with the early to late childhood phenotype. The first signs of the disease were gait disturbances at 4, 2 and 6 years of age, respectively. Neurological examination showed mild tremor of hands and head, truncal ataxia, dysarthria, and hypotonia, after several years followed by spasticity. The course of the disease was slowly progressive. Intellectual abilities are relatively spared. The MRI showed diffusely abnormal white matter of the cerebral hemispheres. The FLAIR images revealed rarefaction of the affected white matter with some stripe-like structures, suggesting the presence of remaining tissue strands. The abnormalities were most pronounced with the middle sister, who had the earliest onset of the disease. A homozygous point mutation in the EIF2B2 gene was found, 638A>G. Both the parents were found to be carriers of this mutation. This is the first description of a Polish family with VWM.

Adolescent↗

PubMed2006

Ultrastructural picture of blood vessels in muscle and skin biopsy in CADASIL.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is an inherited systemic vascular disorder affecting mainly the central nervous system. We performed detailed ultrastructural examination of the small vessels in the skin and skeletal muscle of a 51-year-old patient with bilateral cerebral white matter lesions, who had a history of two ischaemic strokes. The arterioles were characterized by degeneration and loss of vascular smooth muscle cells (VSMCs). GOM deposits, varied in size and shape, were located in the neighbourhood of the smooth muscle cells, often within an infolding of the cell membrane. No apparent correlations between presence, size or number of GOM deposits and damage severity of vascular smooth muscle cells were seen. Moreover, in some capillaries there were GOM deposits which were seen in the basement membrane near pericytes and endothelial cells. On the other hand, lesions of VMSCs and/or endothelial cells were also visible on the sections of blood vessels devoid of GOM deposits. Genetic tests detected a mutation in exon 4 of the Notch3 gene. It confirmed the initial diagnosis which had been suggested on the basis of the clinical and MRI findings.

Biopsy↗

PubMed2005

Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency.

A retrospective, multicenter study of 180 children with cytochrome c oxidase (COX) deficiency analyzed the clinical features, prognosis, and molecular bases of the COX deficiency. Clinical symptoms including failure to thrive, encephalopathy, hypotony, Leigh syndrome, cardiac involvement, and hepatopathy appeared in most patients early after birth or in early childhood. Two thirds of all children died. Biochemical examination revealed an isolated COX deficiency in 101 children and COX deficiency combined with disturbances of other respiratory chain complexes in 79 children. Blood and cerebrospinal fluid lactate increased in 85% and 81% of examined cases, respectively. Pathogenic mutations in mitochondrial or nuclear DNA were established in 75 patients. Mutations in surfeit locus protein 1 gene (SURF1) were found in 47 children with Leigh syndrome; 2bp deletion 845-846delCT was found in 89% of independent alleles. Mutations in a mitochondrial copper-binding protein (SCO2) gene were found in nine children with encephalomyopathy and/or cardiomyopathy; all of them were homozygotes or heterozygotes for 1541G>A mutation. Different mitochondrial DNA (mtDNA) deletion or depletion were found in nine children, mtDNA mutation 3243A>G in six, mtDNA mutation 8363G>A in two children with Leigh syndrome and mtDNA mutations 8344A>G, and 9205-9206delTA in one child each. COX deficiency represents a heterogeneous group of diseases with unfavorable prognosis. Marked prevalence of two nuclear DNA mutations (845-846delCT in the SURF1 gene and 1541G>A in the SCO2 gene) associated with COX deficiency in a Slavonic population suggests the existence of regional differences in the genetic basis of COX deficiency.

Adolescent↗

PubMed2005

MRI of a family with leukoencephalypathy with vanishing white matter.

Leukoencephalopathy with vanishing white matter (VWM) is a newly described entity with characteristic MRI features. We report the cranial MRI findings in three sisters with slowly progressive neurological deterioration. The MRI showed symmetrical diffuse abnormalities of cerebral white matter with hypointensity on FLAIR images. The diagnosis of leukoencephalopathy with VWM was made on the basis of genetic analysis.

Adolescent↗

PubMed2005

Infantile mitochondrial leucodystrophy - a case report.

We retrospectively analyzed a case of a 7-month-old infant with a delay of psychomotor development, slow pupillary light reflexes, horizontal nystagmus, spasticity and bilateral optic nerve atrophy. At the end of life there were problems with swallowing. Ventriculography showed widening of the lateral ventricles and atrophy in the frontal lobes. EEG revealed generalized changes. Clinically, leucodystrophy was diagnosed. General autopsy revealed cardiac hypertrophy. Neuropathological picture showed orthochromatic leucodystrophy with some features characteristic of neuropathology of mitochondrial disease: capillary hyperplasia and hypertrophy, spongiosis and symmetrical, bilateral damage of brain stem structures. The last one is characteristic of Leigh syndrome. Electron microscopic evaluation showed abnormal mitochondria, myelin and neurofibrils destruction. Hypertrophy of the heart may be also connected with mitochondrial disease.

Brain↗

PubMed2004

Rapid-onset dystonia-parkinsonism: a fourth family consistent with linkage to chromosome 19q13.

Rapid-onset dystonia-parkinsonism (RDP, DYT12, MIM 128235) is a rare autosomal dominant movement disorder characterized by abrupt onset of slow, dystonic movements and prominent bulbar features. Three families and 1 isolated case have been described in the literature, and linkage to markers on chromosome 19q13 have been reported. Here, we describe the clinical features in a fourth family (the second in Europe) with 4 affected members, suggesting that RDP may be misdiagnosed for years and/or may mimic other dystonic/parkinsonian syndromes. By using haplotype analysis, we show that the family is consistent with linkage to markers on chromosome 19q13.

Adolescent↗

PubMed2004

Neurodegenerative disease in infants with multiple congenital malformations--report of two cases.

During embryogenesis, about 40% of genes are involved in the development of the central nervous system (CNS). The same genes support the integrity and function of brain cells in humans. Birth defects cause different changes in genetic material during embryogenesis. They may also be responsible for precocious death of cells in postnatal period. We studied cases of two infants with similar congenital defects (prenatal onset growth deficiency, coloboma of iris, epicanthal folds, low set ears, clinodactyly of Vth fingers). The infants died at age 9 and 10 months with signs and symptoms of progressive CNS degeneration. In one case, chromosomal aberration was detected (4pter). Neuropathologicaly, there were small for the age brains, atrophy of cerebral cortex, white matter and basal ganglia (mainly nucleus caudatus) with loss of neurones, spongiosis and hypertrophic astroglia reaction as well as atrophy of cerebellar cortex. Severe damage of white matter was seen. We suggest that such cases are natural models for investigations of the role of genes in embryogenesis and pathogenesis of neurodegenerative diseases.

Abnormalities, Multiple↗

PubMed2002

Diversity of clinical symptoms in A3243G mitochondrial DNA mutation (MELAS syndrome mutation).

BACKGROUND: MELAS (mitochondrial myopathy, lactic acidosis and stroke-like episodes) is one of the most common mitochondrial encephalomyopathies. MATERIAL/METHODS: We present four children with A3243G MELAS mtDNA mutation and give a summary of clinical MELAS symptoms reported in the literature. Serum lactate elevation, mosaic pattern of COX deficit and decreased activity of complex I and IV in the muscle biopsy were found in all cases. RRFs were recognized in three out of four. RESULTS: The main features seen in all our patients were poor growth and fatigability with muscle weakness. All presented epileptic jerks of various character, some deformation features (recurrent pretibial and peritarsal edema, large swollen-looking hands and feet, hypertelorism and protruding ears) and some cutaneous lesions (atopic dermatitis, local melanoderma, asymmetric vascular dilatation). Stroke-like episodes, multihormonal hypopituitarism, sensorineural hypoacusis, pigmentary retinal degeneration, intracranial calcification, heart involvement, recurrent vomiting or abdominal pain were seen only in individual cases. The homonymous hemianopia frequently reported in the literature was not a feature of our patients. One of them suffered from nonspecific sialoadenitis never mentioned in the literature. CONCLUSIONS: Morphological, enzymatic and molecular investigations of a muscle biopsy sample should be undertaken to improve early MELAS detection in patients with any multiorgan disease associated with serum lactate elevation.

Age of Onset↗

PubMedDate not supplied

[Clinical and genetic study of juvenile form of Huntington's disease].

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by high instability and extension of CAG sequences within the coding region of IT15 gene. It affects both sexes and age at onset of the disease may be different but usually occurs in midlife. The term Juvenile Huntington's disease is generally applied to 10% of the cases with onset before 20. We present clinical features and results of DNA analysis in 16 patients from 14 families aged 9 to 36. The age of onset was between 5 to 20 years; duration of the disease was from 2 to 16 years. In 10 cases the mutated gene was transmitted by the affected father; only in two cases by the mother. In all cases anticipation manifested by earlier onset of the disease in subsequent generations and expansion of CAG repeats was documented. The number of CAG repeats was between 50 and 92 (mean 67.3). Progressive mental deterioration, declining school performance, hyperactivity and emotional disturbances were the first symptoms of juvenile HD. Neuropsychological assessment showed mean IQ in Wechsler test 59.6 and Mini-Mental State Examination scores 22.8. Rigidity and bradykinesia were predominant features in the cases with juvenile onset, the remaining ones developed choreatic movements. Three persons had epileptic seizures; two (both females) revealed behaviour and psychiatric disturbances. Amplitudes of somatosensory evoked potentials, visual evoked potentials and brainstem auditory evoked potentials were markedly reduced. MRI of the brain showed atrophy of heads of the caudate nuclei, putamen and globus pallidus.

Adenine↗

PubMedDate not supplied

[MELAS--mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome--two cases confirmed by biochemical and molecular investigations. Differential diagnosis of stroke causes].

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a maternally inherited multisystem disease caused by mutations of the mitochondrial DNA. The characteristic clinical features are: encephalopathy manifesting as dementia and seizures, stroke-like episodes at young age (usually < 40), lactic acidosis and myopathy with ragged-red fibres. Other frequent manifestations include: sensorineural deafness, diabetes, hypoparathyroidism, peripheral neuropathy and cardiomyopathy. We present two patients with MELAS who were diagnosed 4 and 9 years respectively following the onset of the disease despite the characteristic clinical pictures. The differential diagnostics of inborn and acquired disorders causing stroke is included. We regard that mitochondrial diseases are still insufficiently known and are frequently misdiagnosed. The knowledge is indispensable for establishing diagnosis and accurate genetic counselling. Although there is no specific therapy for mitochondrial diseases to date, coenzyme Q and various vitamins as well as moderate degree exercise might be recommended.

Adolescent↗