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Biomedical subjects

K Fumić

Publications and source records attributed to K Fumić.

11 recordsLinked to original sources
PubMed2006

Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations.

Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months the parents noticed short apnoeic crises. She could sit at age 1.5 years, and walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures occurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.

Brain↗
PubMed2005

S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy.

S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine.

Adenosylhomocysteinase↗
PubMed2001

Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome.

Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe extrapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unstable, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosis, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.

Adolescent↗
PubMed2001

Inborn errors of metabolism at the turn of the millennium.

Great progress has been made in the field of hereditary metabolic diseases since the beginning of the past century, when metabolic disorders were not really understood and could only be clinically described. Due to the development of basic sciences and advances in technology, we gained insight in the biochemical and molecular basis of hereditary metabolic diseases. It opened possibilities for their treatment, and also led to the discovery of more metabolic diseases, so today, there are more than 500 inborn errors of metabolism known. Although each of these diseases is quite rare, as a group, however, they affect about 1-2% of newborns and therefore pose a significant health problem. The realization about 50 years ago that some hereditary diseases are curable if timely diagnosed led to the introduction of newborn screening in most countries. Modern technologies in this field allow early diagnosis of more than 30 inborn errors of metabolism. Nevertheless, to diagnose most patients correctly, both selective screening involving teamwork and proper use of current technology are required. In addition to considerable development of diagnostic possibilities, the past decade was marked by advances in the therapy of inborn errors of metabolism. A number of clinical trials are currently underway, promising new and more effective approaches in the treatment of these patients. Thus, the field of inborn errors of metabolism at the beginning of the new millennium continues to be a scientific challenge to modern medicine.

Human Genome Project↗
PubMed1994

Acute upper respiratory tract infections and indications for tonsillectomy in children. I. Immunoglobulin synthesis in the palatine tonsil tissue.

Current viewpoints and practice concerning indications for tonsillectomy are presented. The annual specific risk for upper respiratory infection in children aged up to 15 is 1.1. The risk is higher in the youngest age group, in whom it rises to 1.8, decreasing with age and being lowest among children aged 12-15 years (0.5). The proportion of tonsillitis among acute upper respiratory tract infections is highest in the age group up to 3 years (36.9%); at the age of 4-5 years it is 37.1%, and is lowest among children aged 12-15 years (21.9%). The risk of tonsillitis caused by streptococci is highest among children aged up to 5 years. Statistical significance of differences in the synthesis of immunoglobulins (G, M, A and sA) and lysozymes in the palatine tonsil tissue of tonsillectomized children and healthy volunteers was tested by non-parametric tests for independent samples. Significant differences of the above mentioned syntheses were found in all entities studied. Any contribution to the documentation on the nature and cause of each tonsillitis in childhood is of great clinical value, because it is the only basis for rational consideration of indications for tonsillectomy.

Acute Disease↗
PubMed1993

Lipid-bound sialic acid, prostaglandin E and histamine in head and neck cancer.

Blood concentration of lipid-bound sialic acid (LBSA), prostaglandin E (PGE) and histamine were determined in 37 patients with carcinoma of hypopharynx and larynx (supraglottic and glottic), in 12 non-cancer patients and in 10 healthy subjects. The concentration of LBSA was significantly increased in 94.4% cancer patients preoperatively and fell to somewhat lower levels within 1 month after tumour resection. In patients with complete tumour resection and no tumour recurrences within 2 years, it steadily decreased thereafter, reaching normal levels within 6-24 months after surgery, whereas in patients with tumour recurrences or incomplete tumour resection it rose again within 6 months after tumour resection. Similarly, the concentration of PGE was significantly increased in about two thirds of cancer patients (67.6%) preoperatively, dropped significantly within 1 month after tumour resection and rose again in patients with tumour recurrences. Preoperative histamine concentration was decreased in 24.3% of cancer patients and postoperatively it rose both in patients with or without tumour recurrences.

Adult↗
PubMedDate not supplied

Determination of urine saturation with computer program EQUIL 2 as a method for estimation of the risk of urolithiasis.

To investigate the risk for the development of urolithiasis in 30 children with urolithiasis, 36 children with isolated hematuria, and 15 healthy control children, 24-h urinary excretion of calcium, sodium, oxalate, citrate, sulfate, phosphate, magnesium, urate, chloride, ammonium, and glycosaminoglycans was determined and urine saturation for calcium oxalate was calculated with the computer program EQUIL 2. Compared with controls, children with urolithiasis had significantly increased calcium excretion, oxalate excretion, and urine saturation, whereas children with isolated hematuria had significantly increased calcium excretion only. The best estimation of the relative risk of urolithiasis can be made after urine saturation, using logistic regression. The percentage of patients correctly classified after urine saturation is 85.41% in comparison with 80.95% and 73.81% when the estimation was done by calcium excretion and oxalate excretion, respectively. Using the breakpoint value of 4.29 for urine saturation, it was possible to separate children with increased risk of urolithiasis development from the group of children with isolated hematuria.

Calcium↗
PubMedDate not supplied

[Gangliosides in the serum in lung carcinoma].

In this study, tumor and serum gangliosides were analyzed in patients bearing lung planocellular carcinoma (LPC) before and after operative therapy. Tumor tissue, pathohistologically characterized as carcinoma planocellulare corneum (Ca. epidermoide, type 8070/3, WHO, Geneva, 1981), showed an elevated concentration of gangliosides in comparison to normal tung tissue. The composition of gangliosides in LPC tissue varied from one tumor sample to another, however, two general features were observed. First, LPC contained an increased amount of GM3 and a decreased amount of GD3 gangliosides. Second, an elevated proportion of gangliosides migrating as polysialogangliosides (x3, x5, x6) characterized the majority of LPC tissues. On the other hand, serum of patients with LPC contained an elevated amount of gangliosides (15.8 +/- 0.3 mumols/L) in comparison to control serum (6.1 +/- 0.8 mumols/L) (P less than 0.01). However, analyzing the composition of serum gangliosides by thin-layer chromatography, all serum gangliosides were more or less elevated. By day 21 after the surgical removal of LPC, serum gangliosides dropped by approximately 50% approaching the normal values. It seems that elevated serum gangliosides in LPC patients were secreted from carcinoma cells, because they normalized after surgical removal of LPC. Thus, serum gangliosides might be a useful biochemical tool for diagnosis and therapy monitoring of this carcinoma.

Carcinoma↗
PubMedDate not supplied

[Mucolipidosis type III (case report)].

A six-year-old boy with mucolipidosis type III or pseudo Hurler polydystrophy is described. The disease is manifested by multiple progressive joint contractures, especially of fingers, presenting as claw hands. The diagnosis of mucolipidosis was established after exclusion of rheumatoid arthritis and mucopolysaccharidosis. In serum and medium of cultured skin fibroblasts, high catalytic activities of several lysosomal enzymes with strikingly decreased values in fibroblast homogenate were found. In most lysosomal diseases gene mutations cause reduced or absent activity of a specific enzyme. In mucolipidosis type III, a basic biochemical disorder is the absence of mannose-6-phosphate, a marker that enables lysosomal membrane receptors to recognize lysosomal enzymes. The transport of lysosomal enzymes across the lysosomal membrane is therefore defective. These and several other metabolic diseases are thus categorized as the disorders of the lysosomal enzyme transport. A genetic and biochemical heterogeneity, as well as clinical manifestations, are described in more detail.

Child↗