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Biomedical subjects

O H Skjeldal

Publications and source records attributed to O H Skjeldal.

At least 19 recordsLinked to original sources
PubMed2002

Y chromosome haplogroups in autistic subjects.

The male to female ratio in autism is 4:1 in the global autistic population, but increases to 23:1 in autistic subjects without physical or brain abnormalities.(1) Despite this well-recognised gender difference, male predisposition to autistic disorder remains unexplained and the role of sex chromosomes is still debated. Numerical and structural abnormalities of the sex chromosomes are among the most frequently reported chromosomal disorders associated with autism. However, genome scans have failed to detect linkage on the X chromosome(2,3,4) and this approach cannot study the non-recombining region of the Y chromosome. In this study, we searched for a specific Y chromosome effect in autistic subjects. Using informative Y-polymorphic markers, the Y chromosome haplotypes of 111 autistic subjects from France, Sweden and Norway were defined and compared with relevant control populations. No significant difference in Y-haplotype distribution between the affected and control groups was observed. Although this study cannot exclude the presence of a Y susceptibility gene, our results are not suggestive of a Y chromosome effect in autism.

Autistic Disorder↗
PubMed2001

[Ischemic stroke in children--a diagnostic challenge].

BACKGROUND, MATERIAL AND METHODS: Ischaemic cerebral infarctions are relatively uncommon in childhood, and the aetiologies seen in this age group are different from those commonly seen in adults. This study presents clinical findings, investigation results and outcome in a five-year material collected between 1994 and 1999 in our department. It includes 22 children with ischaemic strokes aged three months to 13 year at the first or only stroke episode. RESULTS: The symptoms caused by ischaemic strokes in this age group vary and are often combined. Motor symptoms dominate, and we found hemiplegia, facial palsy, visual disturbances and reduced consciousness, listed according to decreasing occurrence. Infections and cardiac diseases or procedures were the most common aetiologies, both occurring with 22%. Other groups were autoimmune diseases (14%), malignancies (5%) and dissection of the a. carotis after trauma (5%). None of the patients in this material died as a result of the ischaemic stroke; 27% recovered completely. 41% had light sequela, 18% moderate sequela, and 14% ended up severely disabled. 18% had recurrent stroke episodes. INTERPRETATION: Appropriate examination after stroke in childhood is of great importance, since some of the aetiologies are associated with recurrence risk. Based on our clinical experiences and literature studies, we suggest a plan for diagnostic evaluation and treatment strategies for children who undergo an acute cerebral vascular disease.

Brain Ischemia↗
PubMed2001

Refsum disease, peroxisomes and phytanic acid oxidation: a review.

Refsum disease was first recognized as a distinct disease entity by Sigvald Refsum in the 1940s. The discovery of markedly elevated levels of the branched-chain fatty acid phytanic acid in certain patients marked Refsum disease as a disorder of lipid metabolism. Although it was immediately recognized that the accumulation of phytanic acid is due to its deficient breakdown in Refsum disease patients, the true enzymatic defect remained mysterious until recently. A major breakthrough in this respect was the resolution of the mechanism of phytanic acid alpha-oxidation in humans. In this review we describe the many aspects of Refsum disease from the clinical signs and symptoms to the enzyme and molecular defect plus the recent identification of genetic heterogeneity in Refsum disease.

Humans↗
PubMed2000

Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease.

Refsum's disease (RD) is an inherited neurological syndrome biochemically characterized by the accumulation of phytanic acid in plasma and tissues. Patients with RD are unable to degrade phytanic acid due to a deficient activity of phytanoyl-CoA hydroxyl-ase (PhyH), a peroxisomal enzyme catalysing the first step of phytanic acid alpha-oxidation. To enable mutation analysis of RD at the genome level, we have elucidated the genomic organization of the PHYH gene. The gene is approximately 21 kb and contains nine exons and eight introns. Mutation analysis of PHYH cDNA from 22 patients with RD revealed 14 different missense mutations, a 3 bp insertion, and a 1 bp deletion, which were all confirmed at the genome level. A 111 bp deletion identified in the PHYH cDNA of several patients with RD was due to either one of two different mutations in the same splice acceptor site, which result in skipping of exon 3. Six mutations, including a large in-frame deletion and five missense mutations, were expressed in the yeast Saccharomyces cerevisiae to study their effect on PhyH activity. The results showed that all these mutations lead to an enzymatically inactive PhyH protein.

Amino Acid Substitution↗
PubMed2000

Evidence that Alpers-Huttenlocher syndrome could be a mitochondrial disease.

We report an 11-year-old boy with a slight developmental delay and epilepsy. After he was placed on valproate, he developed hepatic failure and increasing neurologic symptoms, including epilepsia partialis continua, and died. Autopsy findings in liver and cerebrum were consistent with progressive neuronal degeneration of childhood with liver disease, also called Alpers-Huttenlocher syndrome. Ragged red fibers and cytochrome c oxidase negative fibers were present in muscle. These results suggest that Alpers-Huttenlocher syndrome, at least in some patients, is a mitochondrial disease.

Cerebral Cortex↗
PubMed1998

Childhood autism: the need for physical investigations.

In this paper the results of an extensive medical investigation of 25 children with childhood autism are presented and compared with those found in a group of non-autistic individuals matched for sex, age and intellectual level, all referred for developmental deviancy of unknown etiology. The examination included a psychiatric assessment and a neurological examination in addition to neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the clinical examination macrocephaly was found only among the autistic individuals, while the frequency of pathological cerebral CT and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group. All the other pathological findings were found to occur with the same frequency in the two groups. Except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism. Based on the present findings, ordinary procedures for assessment of developmentally delayed children should be followed. This should include a systematic clinical neuropaediatric examination, an assessment of vision and hearing and a chromosome study, including that for fragile X.

Adolescent↗
PubMed1997

Rett syndrome: geographic variation in prevalence in Norway.

The prevalence of Rett syndrome is reported for three Norwegian counties (Rogaland, Ostfold and Nordland). The total number of females between 3 and 19 years of age in these counties was 96,920, and among these 21 females with Rett syndrome were identified, yielding a prevalence rate for Rett syndrome of 2.17 per 10,000 girls. One reason for this comparatively high prevalence rate might be that the full spectrum of Rett syndrome variants was included. The quality of the health care system and the awareness of Rett syndrome and its variants among Norwegians physicians also make it unlikely that many case were missed. However, the high total prevalence was caused by a statistically significant larger number of girls with Rett syndrome in Rogaland than in the other two counties. Sixteen of the girls were identified in Rogaland county, which gives a prevalence rate for this county of 3.77 per 10,000 girls. The prevalence rates in the two other counties were 1.05 and 0.77 per 10,000 girls. The geographical distribution of girls with Rett syndrome in Rogaland is probably due to genetic clustering. Geographical mobility in Norway is limited and many families have lived in the same geographical area for generations. An explanation based on genetic clustering is also supported by the fact that several of the girls with Rett syndrome in Rogaland county are known to be related.

Adolescent↗
PubMed1997

Medium chain acyl-CoA dehydrogenase deficiency and fatal valproate toxicity.

A boy with delayed psychomotor development, attention deficit disorder, and therapy-resistant epilepsy was treated with valproate. The patient died of liver failure after 4 months of valproate treatment. Postmortem investigation of cultured fibroblasts suggested medium chain acyl-CoA dehydrogenase deficiency, an unexpected finding since the boy had not presented typical manifestations of this disease. Because medium chain acyl-CoA dehydrogenase is an important enzyme in the beta-oxidation of fatty acids, our patient probably had a genetically reduced tolerance to valproate. This drug should be omitted in the treatment of seizures in patients with possible medium chain acyl-CoA dehydrogenase deficiency.

Acyl-CoA Dehydrogenase↗
PubMed1997

Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.

Refsum disease is an autosomal-recessively inherited disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells in the CSF. All patients exhibit accumulation of an unusual branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), in blood and tissues. Biochemically, the disease is caused by the deficiency of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal protein catalyzing the first step in the alpha-oxidation of phytanic acid. We have purified PhyH from rat-liver peroxisomes and determined the N-terminal amino-acid sequence, as well as an additional internal amino-acid sequence obtained after Lys-C digestion of the purified protein. A search of the EST database with these partial amino-acid sequences led to the identification of the full-length human cDNA sequence encoding PhyH: the open reading frame encodes a 41.2-kD protein of 338 amino acids, which contains a cleavable peroxisomal targeting signal type 2 (PTS2). Sequence analysis of PHYH fibroblast cDNA from five patients with Refsum disease revealed distinct mutations, including a one-nucleotide deletion, a 111-nucleotide deletion and a point mutation. This analysis confirms our finding that Refsum disease is caused by a deficiency of PhyH.

Adult↗
PubMed1997

Macrocephaly, epilepsy, autism, dysmorphic features, and mental retardation in two sisters: a new autosomal recessive syndrome?

We report two sisters with macrocephaly, epilepsy, and severe mental retardation. The first child was a 14 year old girl born at term after a normal pregnancy, with birth weight 3600 g and occipitofrontal circumference (OFC) 36 cm (75th centile). Her head size increased markedly during the first six months of life, and was later stable at 2-3 cm above the 97.5th centile. Her development was characterised by psychomotor delay, epilepsy, and autistic features. Her face appeared mildly dysmorphic with a large forehead, short philtrum, and bushy eyebrows. Her younger sister was also born at term with birth weight 2600 g and OFC 34 cm (25th centile). She also developed postnatal macrocephaly with OFC 2 cm above the 97.5th centile and the same mild dysmorphic facial features as her sister. Her development was also characterised by psychomotor delay, autistic features, and epilepsy. In addition, she suffered from coeliac disease. She died unexpectedly at the age of 5 years, probably from an epileptic attack. Necropsy confirmed megalencephaly but no other pathological changes were found. The clinical features in these two sisters do not fit with any known syndrome and may represent a previously unrecognised autosomal recessive disorder.

Abnormalities, Multiple↗
PubMed1996

Vision, cognition and developmental characteristics of girls and women with Rett syndrome.

Forty-two females with Rett syndrome, aged 2.5 to 47 years, were assessed with the Teller Acuity Cards and a new version of the Fagan test for age 2 years and above, and their parents were interviewed about the children's communication skills. The visual function of the subjects indicated arrested development, and they scored significantly lower on the Fagan test than a normal comparison group. Their visual processing and memory deteriorated somewhat with age, while those of the comparison group showed a slight increase. Both age at onset of Rett syndrome symptomatology and speech measures were inversely correlated with visual processing and memory, indicating that age at recession may have differential consequences for different functions. Among the subjects, persistent looking was associated with low cognitive function. The results have implications for intervention, and demonstrate that the paradigm of preferential looking may be useful in cognitive assessment of females with Rett syndrome.

Adolescent↗
PubMed1995

[Neuronal migration disorders. Radiological and clinical aspects].

Neuronal migration disorders can cause congenital cerebral malformations during the third and fourth months of gestation. They are usually classified as agyria, pachygyria, schizencephaly, polymicrogyria and heterotopic gray matter. The best diagnostic tool for detecting neuronal migration disorders is magnetic resonance imaging (MRI). Frequently, the migration disorders are associated with epilepsy, psychomotor retardation and cerebral palsy, and patients with these symptoms should always be investigated by cerebral MRI. In this article we discuss radiologic and clinical aspects in the case of six persons with different categories of migration disorders.

Abnormalities, Multiple↗
PubMed1995

Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings--a new recessive syndrome?

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy. The activity of methylmalonyl-CoA mutase and the overall assay of propionic acid metabolism in cultured fibroblasts were normal. The primary defect in this probably new autosomal recessive disorder associated with methylmalonic aciduria is currently not known.

Adult↗
PubMed1994

[Adrenoleukodystrophy--clinical, biochemical and therapeutic aspects].

X-linked adrenoleukodystrophy is a metabolic disorder with broad clinical variations. The disease may be considered as a differential diagnosis in the case of encephalopathy, polyneuropathy, multiple sclerosis-like syndromes and adrenal insufficiency with unknown etiology. The most common form of adrenoleukodystrophy is lethal and starts with dementia in boys under ten years of age. The genetic defect is located to the Xq28 region and codes for a protein which regulates the transport of beta-oxidation enzymes in the peroxisomes. A defect of this protein seems to cause the accumulation of very long-chain fatty acids. This defect can be measured easily in the serum from patients and female carriers. Therapeutic attempts, for instance with Lorenzo's oil, in order to reduce serum level of very long-chain fatty acids, have not proven to be effective in already neurologically symptomatic patients. At present, the treatment of choice seems to be bone marrow transplantation in presymptomatic boys.

Adolescent↗