Papers by Vladimir Sarnavka
Acta medica Iugoslavica, 1983
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Lijec̆nic̆ki vjesnik
Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical ph... more Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme ...
Lijec̆nic̆ki vjesnik
Glutaric aciduria type 1 (GA 1) is a preventable cause of acute brain damage in early childhood, ... more Glutaric aciduria type 1 (GA 1) is a preventable cause of acute brain damage in early childhood, leading to a severe dystonic-dyskinetic disorder. Typically between 6 and 18 months of age, a non-specific illness such as respiratory or gastrointestinal infection or immunization leads to encephalopathic crisis, usually resulting in degeneration of the putamen and caudate. GA 1 is an autosomal recessive disease of catabolism of amino acids lysine, hydroxylysine and tryptophane leading to accumulation of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Recognition of this biochemical disorder before the brain has been injured is essential to the outcome. Diagnosis depends upon the recognition of relatively non-specific physical findings such as hypotonia, tremor, irritability and macrocephaly, and on urinary organic acids analysis. The diagnosis may also be suggested by characteristic findings of neuroimaging. Specific management includes pharmacological doses of 1-carnitine a...
Lijec̆nic̆ki vjesnik
Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and ... more Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and early infancy periods. Althought the disease is relatively rare with incidence of about 1:25 000-50 000 live births, the importance of the disease should not be underestimated. Namely, prompt recognition and management of patients with CHI is essential, if permanent neurological impairment is to be avoided. CHI is caused by mutations in one of the 7 genes involved in the regulation of insulin secretion in pancreatic beta-cells. It is important to introduce specific medical therapy as soon as diagnosis is established. Severe, neonatal forms of CHI are often resistant to medications, thus they require surgical procedure. The preoperative genetic testing and scintigraphy are indicated to distinguish histological subtypes of the disease (focal vs. diffuse CHI). Patients with focal disease are usually cured after pancreatic resection, while diffuse disease has much worse prognosis. This manus...
Acta medica Iugoslavica, 1990
In 1985 a newborn screening programme for the detection of congenital hypothyreosis was introduce... more In 1985 a newborn screening programme for the detection of congenital hypothyreosis was introduced in Croatia in addition to the already existing one for phenylketonuria. The paper delineates the organization of the screening programme, the method used, and the first results. Clinical manifestations, somatic and mental development, as well as laboratory findings of the first eleven children with congenial hypothyroidism detected by the screening programme and followed-up regularly are presented in more detail.
Collegium antropologicum, 2010
Pallister Killian syndrome (PKS) is a rare genetic disorder caused by tetrasomy of the short arm ... more Pallister Killian syndrome (PKS) is a rare genetic disorder caused by tetrasomy of the short arm of chromosome 12, revealed usually in mosaic distribution of an extra i (12) (p10) chromosome in fibroblasts. The syndrome presents with a recognizable pattern of findings including pigmentary skin changes, coarse face, high forehead, sparse anterior scalp hair, hypertelorism, seizures and progressive psychomotor developmental delay. It was first described independently by Pallister in 1977 and by Killian and Teschler-Nikola in 1981. We report a case of 21 month old girl with PKS and significant overgrowth. Cytogenetic analysis was performed using the GTG banding technique. The karyotype of cultured lymphocytes was normal. The karyotype from skin fibroblasts was established as mosaic tetrasomy of 12p 47,XX,+i (12) (p10)/46,XX. The origin of the extra marker chromosome was determinated by fluorescence in situ hybridization with chromosome 12 specific DNA probes confirming that supernumera...
Collegium antropologicum, 2009
Hypophosphatasia is a metabolic bone disease characterized by bone and teeth hypomineralization d... more Hypophosphatasia is a metabolic bone disease characterized by bone and teeth hypomineralization due to defective function of tissue-nonspecific alkaline phosphatase (TNSALP). The disorder is caused by various mutations in the TNSALP gene localized on short arm of chromosome 1. Infantile hypophosphatasia is a severe form of the disease inherited as an autosomal recessive trait which presents before age of six months and often has fatal outcome. We report a patient with typical clinical course for infantile hypophosphatasia who was homozygous for the c.1402G>A mutation. The same mutation has been previously associated with a more severe perinatal form also in a Croatian family what indicates a possible common ancestral origin and phenotypic variability potential of c.1402G>A mutation of TNSALP gene.
Paediatria Croatica, 2013
Journal of Inherited Metabolic Disease, 2001
Succinyl-CoA:acetoacetate transferase (SCOT) (EC 2.8.3.5) is a mitochondrial enzyme necessary for... more Succinyl-CoA:acetoacetate transferase (SCOT) (EC 2.8.3.5) is a mitochondrial enzyme necessary for ketone body utilization in peripheral tissues. Its de¢ciency (McKusick 245050) has been reported in a limited number of patients and is characterized by recurrent ketoacidotic crises that can be life threatening . Here we report a new patient whose clinical course thus far is benign despite very low residual activity.
by Urh Groselj, Maja Djordjevic, Natalija Angelkova, Hajrija Maksic, Florentina Moldovanu, Vladimir Sarnavka, Aleksei Savov, Biljana Suzic, Radka Tincheva, Natalia Usurelu, Alma Toromanovic, and M. Samardzic Molecular Genetics and Metabolism, 2014
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.
Neuropediatrics, 2009
We have analyzed the morphology and dendritic development of neocortical neurons in a 2.5-month-o... more We have analyzed the morphology and dendritic development of neocortical neurons in a 2.5-month-old infant with Walker-Warburg syndrome homozygotic for a novel POMT1 gene mutation, by Golgi methods. We found that pyramidal neurons frequently displayed abnormal (oblique, horizontal, or inverted) orientation. A novel finding of this study is that members of the same population of pyramidal neurons display different stages of development of their dendritic arborizations: some neurons had poorly developed dendrites and thus resembled pyramidal neurons of the late fetal cortex; for some neurons, the level of differentiation corresponded to that in the newborn cortex; finally, some neurons had quite elaborate dendritic trees as expected for the cortex of 2.5-month-old infant. In addition, apical dendrites of many pyramidal neurons were conspiciously bent to one side, irrespective to the general orientation of the pyramidal neuron. These findings suggest that Walker-Warburg lissencephaly is characterized by two hitherto unnoticed pathogenetic changes in the cerebral cortex: (a) heterochronic decoupling of dendritic maturation within the same neuronal population (with some members significantly lagging behind the normal maturational schedule) and (b) anisotropically distorted shaping of dendritic trees, probably caused by patchy displacement of molecular guidance cues for dendrites in the malformed cortex.
Molecular Genetics and Metabolism, 2009
Specific mutations in the gene encoding phenylalanine hydroxylase (PAH), located on chromosome 12... more Specific mutations in the gene encoding phenylalanine hydroxylase (PAH), located on chromosome 12q22-24.1, are linked to tetrahydrobiopterin (BH 4 ; sapropterin)-responsive phenylketonuria (PKU). Diagnosis is usually done through the newborn screening for PKU, followed by a BH 4 loading test. So far, more than 60 mutant alleles, presenting with a substantial residual PAH activity (average $47%), were identified in more than 500 patients worldwide. We investigated the predictive value of BH 4responsive PAH mutations in Croatian population. From a group of 127 PKU patients, 62 were selected (based on the genotype) as potentially BH 4 -responsive and 39 loaded with BH 4 (20 mg/kg). The overall frequency of BH 4 -responsiveness (>30% blood phenylalanine reduction within 24 h) was 36% (14 out of 39 patients with 23 different genotypes), significantly less than expected. The best responders were patients with mild hyperphenylalaninemia (4/4; 100%), followed by mild PKU (8/9; 89%), and classical PKU (2/26; 8%). The most common BH 4 -responsive genotypes were p.E390G/p.R408W and p.P281L/ p.E390G. These genotypes correspond for approximately >30% residual PAH activity. The p.E390G mutation was 100% associated with BH 4 -responsiveness, regardless of the second allele (p. R408W, p.P281L, p.F55Lfs, p.L249P). With regard to the predicted relative PAH activity of recombinantly expressed mutant alleles, there was a significant (p < 0.002) difference between BH 4 -responders and non-responders.
Journal of Inherited Metabolic Disease, 2006
Word counts: Text: 707 (including summary) Abstract: 250 Number of figures and tables: 0 Details ... more Word counts: Text: 707 (including summary) Abstract: 250 Number of figures and tables: 0 Details of funding: This research was supported by grants 0108016 (Republic of Croatia) and MSM 002160806 (Czech Republic).
Human Mutation, 2003
We present the results of a comprehensive analysis of mutations, polymorphisms and haplotypes in ... more We present the results of a comprehensive analysis of mutations, polymorphisms and haplotypes in the phenylalanine hydroxylase ( PAH) gene in 39 Croatian families with phenylketonuria (PKU). A total of 21 disease-causing mutations was identified on 78 out of 79 independent chromosomes. The commonest mutation, R408W on haplotype 2 was found with a relative frequency of 37 %. P281L accounted for 11 %, R261Q and E390G each for 9 % of mutant chromosomes. There were three novel mutations: L249P (c.746T>C) in exon 7, IVS8+2T>C (c.912T>C) in intron 8, and F402L (c.1206T>G) in exon 12 of the PAH gene. Two known PKU mutations were found in cis on the same chromosome in one family, highlighting the need to perform full mutation scanning in recessive disease genes for molecular diagnosis even if two known mutations have been identified in a patient. This is the first comprehensive report on PKU mutations in southeastern Europe, adding to the growing bulk of molecular data for population genetic investigations.
European Journal of Pediatrics, 2000
European Journal of Pediatrics, 1991
Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic ner... more Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.
European Journal of Paediatric Neurology, 2011
S-adenosylhomocysteine hydrolase deficiency is a multisystemic inherited disorder in methionine m... more S-adenosylhomocysteine hydrolase deficiency is a multisystemic inherited disorder in methionine metabolism recently described by our group (Barić I, et al. PNAS 2004;101:4234-9). Biochemical hallmarks of the disease are remarkably elevated plasma Sadenosylmethionine (AdoMet) and particularly S-adenosylhomocysteine (AdoHcy) in presence of normal or nearly normal plasma homocysteine. Hypermethioninemia was not uniformly present. Abnormal methylation due to inhibition of numerous methyltransferases by decreased AdoMet to AdoHcy ratio [the AdoMet/AdoHcy ratio is a poor criterion to use -see JD Finkelstein, Clin Chem Lab Med 45, 1694-1699, 2007 is being considered as the main pathogenetic mechanism. Since this mechanism seems to be involved in many, more common pathological conditions, like all associated with hyperhomocysteinemia (spinal dysraphism , [is this really an abnormality associated with hyperhomocysteinemia??] early onset vascular disease, cognitive disorders in elderly, etc.) AdoHcy hydrolase deficiency could be a useful natural model for studying these conditions. We participated in the diagnostic work-up in all eight patients reported so far. All had neurological and muscular signs and symptoms. Congenital myopathy with high creatine kinase was present in all of them, the majority had delayed psychomotor development and attention deficit-hyperactivity disorder, while some had delayed myelination. The two most severely affected, who died in early infancy, had developmental brain anomalies in the posterior fossa-mega cisterna magna and hypoplasia of ventral pons and cerebellar components. These observations suggest that AdoHcy hydrolase deficiency should be included in differential diagnosis in all children with unexplained signs and symptoms mentioned above, in particular since the disorder seems to be at least partly treatable by dietary and other means. We stay at disposition for related diagnostic assistance and research ([email protected]).
European Journal of Paediatric Neurology, 2011
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Papers by Vladimir Sarnavka