Pinar Ozand

Bio: Pinar Ozand is an academic researcher from Yıldız Technical University. The author has contributed to research in topics: Propionic acidemia & Gangliosidosis. The author has an hindex of 26, co-authored 160 publications receiving 2273 citations. Previous affiliations of Pinar Ozand include King Faisal Specialist Hospital & Research Centre & King Khalid University.

Biotin-responsive basal ganglia disease: a novel entity.

Abstract: We describe a novel, biotin-responsive basal ganglia disease in 10 patients. At onset, it appears as a subacute encephalopathy, with confusion, dysarthria and dysphagia with occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progresses to severe cogwheel rigidity, dystonia and quadriparesis. These symptoms disappear within a few days if biotin (5-10 mg/kg/day) is administered, and there are no neurological sequelae. They reappear within 1 month if biotin is discontinued. Patients diagnosed late, or who have had repeated episodes, suffer from residual symptoms such as paraparesis, mild mental retardation or dystonia. The numerous biochemical studies of intermediary metabolism, like the autoimmune and toxicological studies, enzyme assays including biotinidase, carboxylase and lysosomal activities, and bacterial and viral studies were all normal. The aetiology may be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiological abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This was present during the initial acute encephalopathy and remained unchanged during follow-up of 3-10 years. Although its aetiology is unknown, it is important to recognize this disease, since its symptoms may be reversed and the progression of its clinical course prevented simply by providing biotin.

Multiple displacement amplification on single cell and possible PGD applications

Abstract: Multiple displacement amplification (MDA) is a technique used in the amplification of very low amounts of DNA and reported to yield large quantities of high-quality DNA. We used MDA to amplify the whole genome directly from a single cell. The most common techniques used in PGD are PCR and fluorescent in-situ hybridization (FISH). There are many limitations to these techniques including, the number of chromosomes diagnosed for FISH or the quality of DNA issued from a single cell PCR. This report shows, for the first time, use of MDA for single cell whole genome amplification. A total of 16 short tandem repeats (STRs) were amplified successfully with a similar pattern to the genomic DNA. Furthermore, allelic drop out (ADO) derived from MDA was assessed in 40 single cells by analysing (i) heterozygosity for a known beta globin mutation (IVSI-5 C-G) and by studying (ii) the heterozygous loci present in the STRs. ADO turned out to be 10.25% for the beta globin gene sequencing and 5% for the fluorescent PCR analysis of STRs. Moreover, the amplification accuracy of MDA permitted the detection of trisomy 21 on a single cell using comparative genome hybridization-array. Altogether, these data suggest that MDA can be used for single cell molecular karyotyping and the diagnosis of any single gene disorder in PGD.

Atlas of metabolic diseases

Abstract: In a field where even experts may find that years have elapsed since they last encountered a child with a given disorder, it is essential for the clinician to have a comprehensive source of practical and highly illustrated information covering the whole spectrum of metabolic disease to refer to. The second edition of this highly regarded book, authored by three of the foremost authorities in pediatric metabolic medicine, fulfils this need by providing an invaluable insight into the problems associated with metabolic diseases. For ease of reference, Atlas of Metabolic Disease is divided into sections of related disorders, such as disorders of amino acid metabolism, lipid storage disorders and mitochondrial diseases, with an introductory outline where appropriate summarizing the biochemical features and general management issues. Within sections each chapter deals with an individual disease, starting with a useful summary of major phenotypic expression and including clear and helpful biochemical pathways, identifying for the reader exactly where the defect is occurring. Throughout the book, plentiful photographs, often showing extremely rare disorders, are an invaluable aid to diagnosis.

Topical Review Article: Organic Acidurias: A Review. Part 1

Abstract: Organic acidemias are disorders of intermediary metabolism that lead to accumulation of organic acids in biologic fluids, disturb acid-base balance, and derange intracellular biochemical pathways. Their clinical presentation reflects the resultant systemic disease and progressive encephalopathy. While in some organic acidemias, disturbed acid-base metabolism is the predominant presenting feature, in others it is less prominent or even absent. The etiologies of the more than 50 different phenotypes include impaired metabolism of branched-chain amino acids, vitamins, glucose, lipids, glutathione, and γ-aminobutyric acid and defects of oxidative phosphorylation. Most organic acidemias present with neurologic manifestations, which include acutely or subacutely progressive encephalopathy that involves different parts of the nervous system. The age of presentation and the associated systemic, hematologic, and immune findings provide additional guidelines for differential diagnosis. We summarize major organic ac...

Prevalence of lysosomal storage disorders.

Abstract: ContextLysosomal storage disorders represent a group of at least 41 genetically distinct, biochemically related, inherited diseases. Individually, these disorders are considered rare, although high prevalence values have been reported in some populations. These disorders are devastating for individuals and their families and result in considerable use of resources from health care systems; however, the magnitude of the problem is not well defined. To date, no comprehensive study has been performed on the prevalence of these disorders as a group.ObjectiveTo determine the prevalence of lysosomal storage disorders individually and as a group in the Australian population.DesignRetrospective case studies.SettingAustralia, from January 1, 1980, through December 31, 1996.Main Outcome MeasureEnzymatic diagnosis of a lysosomal storage disorder.ResultsTwenty-seven different lysosomal storage disorders were diagnosed in 545 individuals. The prevalence ranged from 1 per 57,000 live births for Gaucher disease to 1 per 4.2 million live births for sialidosis. Eighteen of 27 disorders had more than 10 diagnosed cases. As a group of disorders, the combined prevalence was 1 per 7700 live births. There was no significant increase in the rate of either clinical diagnoses or prenatal diagnoses of lysosomal storage disorders during the study period.ConclusionsIndividually, lysosomal storage disorders are rare genetic diseases. However, as a group, they are relatively common and represent an important health problem in Australia.

Understanding 'Global' Systems Biology: Metabonomics and the Continuum of Metabolism

Abstract: To apply genomic knowledge effectively in drug discovery, mechanistic connectivities between genetic variation and disease processes need to be established via systems biology approaches. Humans have hundreds of functionally specialized cell types that interact differentially with environmental factors to influence disease development and to modulate the effects of drugs. Metabonomics can provide a means of modelling these interactions, but the relationships between 'endogenous' metabolic processes (coded in the genome and intrinsic to cellular function) and 'xenobiotic' (foreign compound) metabolism are poorly understood, especially with respect to environmental factors. We present an overview of 'global' mammalian metabolic conversions that should be accounted for in human systems biology models and propose a new probabilistic approach to help understand gene–disease relationships and vexed issues of idiosyncratic drug toxicity.

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Abstract: Background: Over the past decade laboratories that test for metabolic disorders have introduced tandem mass spectrometry (MS/MS), which is more sensitive, specific, reliable, and comprehensive than traditional assays, into their newborn-screening programs. MS/MS is rapidly replacing these one-analysis, one-metabolite, one-disease classic screening techniques with a one-analysis, many-metabolites, many-diseases approach that also facilitates the ability to add new disorders to existing newborn-screening panels. Methods: During the past few years experts have authored many valuable articles describing various approaches to newborn metabolic screening by MS/MS. We attempted to document key developments in the introduction and validation of MS/MS screening for metabolic disorders. Our approach used the perspective of the metabolite and which diseases may be present from its detection rather than a more traditional approach of describing a disease and noting which metabolites are increased when it is present. Content: This review cites important historical developments in the introduction and validation of MS/MS screening for metabolic disorders. It also offers a basic technical understanding of MS/MS as it is applied to multianalyte metabolic screening and explains why MS/MS is well suited for analysis of amino acids and acylcarnitines in dried filter-paper blood specimens. It also describes amino acids and acylcarnitines as they are detected and measured by MS/MS and their significance to the identification of specific amino acid, fatty acid, and organic acid disorders. Conclusions: Multianalyte technologies such as MS/MS are suitable for newborn screening and other mass screening programs because they improve the detection of many diseases in the current screening panel while enabling expansion to disorders that are now recognized as important and need to be identified in pediatric medicine.