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Biomedical subjects

H Pihko

Publications and source records attributed to H Pihko.

At least 55 records · Page 3Linked to original sources
PubMed1995

Palmitate oxidation in muscle mitochondria of patients with the juvenile form of neuronal ceroid-lipofuscinosis.

The finding that the intracellular storage material in juvenile neuronal ceroid lipofuscinosis (JNCL) consists of the subunit c of ATP synthase prompted us to study energy conservation in JNCL patients. The activities of respiratory chain enzymes in isolated muscle mitochondria from 8 JNCL cases were normal, but oxidation of palmitate was reduced in 6 patients. The degree of reduction was related to the age of the patients. None of the patients had clinical symptoms or laboratory findings of impaired energy conservation, which suggest that the reduced palmitate oxidation was not associated with a major defect in fatty acid oxidation.

Adolescent↗
PubMed1995

Diagnosis of fatal infantile defects of the mitochondrial respiratory chain: age dependence and postmortem analysis of enzyme activities.

We studied two diagnostic aspects of fatal infantile defects of the mitochondrial respiratory chain: the age dependence of muscle mitochondrial enzyme activities and the reliability of diagnosis from autopsy samples. In morphologically normal quadriceps muscle samples of 46 children between the ages of 3 days and 15 years, activities of complex I plus III (NADH:cytochrome c oxidoreductase) and complex II plus III (succinate:cytochrome c oxidoreductase) increased 2-fold during the first three years of life, while that of complex II (succinate dehydrogenase), complex IV (cytochrome c oxidase), and citrate synthase did not show significant correlation with age. We suggest that these changes are related to age and stress the importance of strictly age-matched controls when diagnosing a mitochondrial disease of early childhood. The value of autopsy samples in diagnostic studies was evaluated by comparing mitochondrial enzyme activities in quadriceps muscle from autopsies and from surgical biopsies. In quadriceps muscle mitochondria, all the enzyme activities studied remained stable for at least 3 h after death. Using age-matched controls and autopsy samples, we diagnosed a respiratory chain enzyme deficiency in two infants, and the defects were confirmed in cultured skin fibroblasts.

Adolescent↗
PubMed1995

Muscle-eye-brain disease and Fukuyama type congenital muscular dystrophy are not allelic.

Muscle-Eye-Brain disease (MEB) and Fukuyama type congenital muscular dystrophy (FCMD) are clinically similar autosomal recessive diseases, characterized by congenital muscular dystrophy and severe mental retardation, raising the possibility that they might be caused by mutations of the same gene. Recently FCMD was localized to chromosome 9q31-33 by linkage. We performed a linkage study in seven Finnish MEB families with 12 affected patients using markers D9S53, D9S58, D9S59 and HXB. The MEB phenotype was not linked to any of the markers. A multipoint linkage analysis excluded the entire region harboring FCMD. We thus conclude that MEB and FCMD are not allelic.

Adolescent↗
PubMed1995

Primary hypogonadism in females with infantile onset spinocerebellar ataxia.

We recently described an infantile onset spinocerebellar ataxia (IOSCA) in 19 Finnish patients. The classification of hereditary ataxias of unknown etiology is difficult because of the heterogeneity of these diseases. The clinical course of IOSCA is homogeneous. Ataxia, muscle hypotonia, athetosis, and loss of deep tendon reflexes in the legs appeared around the age of 1 year. Ophthalmoplegia and deafness were found by school-age, and sensory axonal neuropathy and optic atrophy by adolescence. An acute crisis with epilepsy was a late manifestation. The female patients had hypogonadism. In order to define the type of hypogonadism and to exclude other endocrine defects we measured serum concentrations of SHBG, DHEAS, prolactine, testosterone/estradiol, FSH and LH in postpubertal patients. ACTH, hCG and GnRH tests were performed to both pre- and postpubertal patients. Growth was analysed, and the brain and pituitary region were examined with magnetic resonance imaging (MRI). The estradiol values were low and FSH and LH values were high in the female patients, which indicates that the hypogonadism was of the hypergonadotropic type. The growth of the female patients was steady without a significant pubertal growth acceleration. The growth and pubertal development of the male patients were normal. The adrenal cortical and thyroidea functions were normal in all patients.

Adolescent↗
PubMed1995

Correlation between the clinical symptoms and the proportion of mitochondrial DNA carrying the 8993 point mutation in the NARP syndrome.

We describe a four-generation family with a maternally inherited mitochondrial disorder. The symptoms were restricted to the CNS and muscle, the most common features being subacute necrotizing encephalomyopathy, cognitive impairment, ataxia, retinitis pigmentosa, infantile spasms, and optic atrophy. A point mutation at the nucleotide 8993 of the gene encoding subunit 6 of the ATP synthase, associated with the neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP) syndrome, was shown to be inherited maternally in this family, and a clear correlation was found between the clinical severity of the disease and the proportion of mutant mtDNA. Analysis of oxidative phosphorylation in mitochondria carrying 80% mutant mitochondrial DNA showed a reduction of the ATP generation rate coupled to substrate oxidation.

Adolescent↗
PubMed1995

Infantile-onset spinocerebellar ataxia: MR and CT findings.

PURPOSE: To report the MR and CT findings in a hereditary disease, infantile-onset spinocerebellar ataxia (IOSCA). METHODS: We studied the brains of 17 patients with infantile-onset spinocerebellar ataxia with CT and/or MR to determine the presence of cerebellar and brain stem atrophy and parenchymal lesions. RESULTS: Cerebellar cortical atrophy was seen in 13 patients. The degree of atrophy correlated with increasing age and clinical deterioration. Brain stem atrophy was seen in 8 patients. It was never severe, and the basis pontis was not flattened even in the most severe cases. Hyperintense lesions were noted within the white matter of cerebellum, in the dentate nuclei, and in the middle cerebellar peduncles in 3 patients. The upper cervical cord was seen in 9 patients and showed mild to moderate atrophy in 4. The basal ganglia and cerebral hemispheres were normal, except in 2 patients transient cortical and subcortical lesions developed during episodes of status epilepticus; mild cortical brain atrophy subsequently developed. CONCLUSION: The brain MR and CT findings of patients with infantile-onset spinocerebellar ataxia correspond to the neuropathologic entities of cerebellar cortical atrophy, olivopontocerebellar atrophy, and spinocerebellar atrophy. The appearance of the findings followed a uniform time sequence from cerebellar cortical atrophy in the early stage of the disease to olivopontocerebellar atrophy and spinocerebellar atrophy in the later stage. The severity of atrophy correlated with clinical deterioration.

Adolescent↗
PubMed1994

Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA).

Infantile onset spinocerebellar ataxia with sensory neuropathy is a new, inherited multisystem disorder discovered in 19 Finnish patients. In order to define the neuropathy of the disease, we measured sensory nerve action potentials and nerve conduction velocities in 18 patients, and recorded somatosensory evoked potentials (SEP) in 10 patients and performed a sural nerve biopsy in 13 patients. The fixed and teased nerve fascicles were examined by light and electron microscopy, and the whole transverse section of a nerve fascicle was photographed and enlarged for morphometric measurements. Our investigation revealed an early onset, rapidly progressive axonal neuropathy: the sensory action potentials were decreased after the age of 2 and a severe loss of mainly large myelinated fibers was found.

Adolescent↗
PubMed1994

MRI of the brain in muscle-eye-brain (MEB) disease.

Muscle-eye-brain (MEB) disease belongs to the spectrum of rare congenital syndromes with migration disorders of the brain and muscular dystrophy, along with the Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy. Their features overlap, and differential diagnosis presents some difficulties. We examined the brain of 10 patients with MEB using high-field MRI and found a uniform pattern consisting of a pachygyria-type cortical migration disorder, septal and corpus callosum defects and severe hypoplasia of the pons in 7 of them.

Adolescent↗
PubMed1994

Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease.

We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.

Adolescent↗
PubMed1994

Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias.

Hereditary ataxias are a heterogeneous group of progressive neurodegenerative disorders characterized by symptoms and signs originating mainly in the CNS. A new representative of this disease group is infantile onset spinocerebellar ataxia, an autosomal recessively inherited syndrome so far reported only in the genetically isolated Finnish population. The etiology of hereditary ataxias still remains unknown, but the gene loci behind many of them have been mapped to different chromosomal regions. We have carried out linkage analyses with markers on the regions of the previously identified ataxia loci to determine whether the infantile onset spinocerebellar ataxia syndrome represents the same allelic disease as any of the previously identified hereditary ataxias. Here we report that the infantile onset spinocerebellar ataxias syndrome does not segregate with any of the markers closely linked to the other hereditary ataxias. Consequently, it represents a genetically distinct disease, the gene locus of which still has to be identified.

Age of Onset↗
PubMed1993

Progressive unilateral hypertrophic myopathy: a case study.

A 12-year-old girl had progressive unilateral muscle hypertrophy limited to the sole, tibialis anterior, and biceps femoris muscles. The affected muscles showed complex repetitive discharges by electromyography, necrosis and variation of fiber size upon histopathological examination, and increased metabolic activity in biochemical studies. The findings suggest a myopathic origin, but the actual cause remains unknown.

Child↗
PubMed1993

Transient ischemic cerebral lesions during induction chemotherapy for acute lymphoblastic leukemia.

Ninety children were treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma during 1986 through 1992 in the Children's Hospital, University of Helsinki, in Finland. During induction chemotherapy, nine of the children had visual hallucinations progressing to confusion and seizure. The symptoms were often preceded by severe constipation and significantly elevated blood pressure. Neuroradiologic examinations showed bilateral cortical or subcortical white matter lesions. Despite the stroke like manifestations, the lesions were reversible. The triangular shape and location of the lesions in the watershed areas between the major cerebral arteries suggest vascular ischemia as the cause.

Adolescent↗
PubMed1993

Quantification of tRNA3243(Leu) point mutation of mitochondrial DNA in MELAS patients and its effects on mitochondrial transcription.

The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcription downstream of the ribosomal RNA (rRNA) genes, thus possibly reducing rRNA synthesis in relation to more distal transcripts. This study presents a family in which maternally transmitted diabetes and MELAS syndrome overlap, and a suggestive correlation between the amount of mutant mtDNA and clinical symptoms is observed. Mutant mtDNA was quantified in several tissues of a newborn infant and the highest amount of mutant mtDNA was found in the placenta, which is promising for the development of genetic counselling in MELAS. The consequences of the MELAS mutation were further studied in cultured clonal myoblasts. We found that the myoblasts with 93% of mutant mtDNA terminate the mitochondrial transcription, resulting in a steady-state amount of 16S rRNA 45 times as high as the more distal transcripts. However, myoblasts with a deletion of mtDNA not involving the transcription termination site had 120 times as much 16S rRNA as the distal transcripts. In both the MELAS myoblasts and in those with a deletion of mtDNA the amount of 16S rRNA increased as the mutant mtDNA increased, suggesting that the production of ribosomal RNAs is a response to the translational defect caused by the mutation. We present evidence here that the MELAS mutation causes a defect in transcription termination, thus leading to no absolute deficiency of ribosomal RNAs, but to a reduced capacity to compensate the defective translation.

Adolescent↗
PubMed1993

T1 rho dispersion imaging of diseased muscle tissue.

T1 rho dispersion, or the frequency dependence of T1 relaxation in the rotating frame, was used for in vivo muscle tissue characterization in 13 patients with primary skeletal muscle disease and in eight normal subjects for comparison. T1 rho dispersion measurements represent a new approach to magnetic resonance tissue characterization, possibly reflecting the macromolecular constituents of tissue. A definite, statistically significant, difference was found between the relative T1 rho dispersion values of normal and diseased muscle tissue. T1 rho dispersion measurements and images may increase the accuracy of identification of diseased muscles. Early identification of affected muscles is important for accurate diagnosis by muscle biopsy.

Adolescent↗
PubMed1992

CNS in congenital muscular dystrophy without mental retardation.

We have evaluated the CNS findings of 30 patients with congenital muscular dystrophy and normal mental development. The intelligence was estimated by psychological testing or school performance. There were more children of above average intelligence than expected. Neuroradiological examination was done to 15/17 patients still alive. White matter changes were seen in five and cerebral atrophy in four patients. Three patients had epilepsy, two mild, one drug resistant. The EEG did not reveal any common pattern, though there were various abnormalities in several children.

Achievement↗