Karmen Bilić

Rupture of the middle cerebral artery aneurysm as a presenting symptom of late-onset Pompe disease in an adult with a novel GAA gene mutation

Report of a patient with late onset Pompe disease caused by a novel GAA gene mutation who presented with subarachnoid hemorrhage due to rupture of the middle cerebral artery aneurysm.

Growth characteristics of channel catfish ovary cells-influence of glucose and glutamine

The growth characteristics and influence of glucose and glutamine on the growth and maintenance of channel catfish ovary (CCO) cells were investigated. Besides glutamine, amino acids threonine, arginine, methionine and serine were found to be essential for CCO cell growth. In the glucose-free medium, glutamine is utilized as energy source and no cell growth limitation was observed. However, the lack of glutamine in culture medium did not stimulate CCO cells to efficient glucose consumption. When both glucose and glutamine were deficient, cell growth was also observed suggesting no rigorous nutritional requirements. Obtained results are useful for further understanding of culture processes using CCO cells.

INTEGRATIVE ALGORITHMS IN THE DIAGNOSTICS OF LYSOSOMAL STORAGE DISEASES INTEGRATIVNI ALGORITMI U DIJAGNOSTICI POREME)AJA U SKLADI(TENJU LIZOZOMA

Summary Lysosomal storage disorders (LSDs) are a clinically heterogeneous group of more than 50 disorders which still represent a challenge in modern medicine. The efficacy of many current and proposed therapies relies heavily upon early detection and treatment prior to the onset of irreversible pathology. Although there are multiple paths and algorithms to a final diagnosis, the diagnostic strategy for LSDs still mostly relies on initial clinical suspicion followed by adequate specialist and laboratory management - a selective screening approach. Despite the fact that the technology of tandem mass spectrometry enables newborn screening, such screening is generally acceptable only for a population at high risk for a certain LSD. As diagnostic testing for these disorders may be difficult, communication between the clinician who has established clinical suspicion and laboratory personnel will help complete this process. Kratak sadržaj Poremećaji u skladištenju lizozoma u kliničkom smislu čine heterogenu grupu više od 50 poremećaja koji još pred stavljaju izazov za modernu medicinu. Efikasnost mnogih postojećih i predloženih terapija u velikoj meri zavisi od rane detekcije i primene terapije pre nego što dođe do razvoja neizle čive patologije. Iako postoje brojni putevi i algoritmi za konačnu dijagnozu, dijagnostička strategija za poremećaje u skladištenju lizozoma i dalje se uglavnom oslanja na početnu kliničku sumnju posle koje sledi adekvatan specijalistički tretman i laboratorijski radpristup selektivnog skrininga. Uprkos činjenici da tehnologija tandem masene spektrometrije omogućava skrining novorođenčadi, takav skrining je generalno prihvatljiv samo za populacije sa visokim rizikom za odre đeni poremećaj u skladištenju lizozoma. Kako dijagnostič ko testiranje za ove poremećaje može biti teško, komunikacija između kliničara koji je ustanovio kliničku sumnju i osoblja u laboratoriji doprineće uspešnom okončanju ovog procesa.

Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families

Primary 5-oxoprolinuria (pyroglutamic aciduria) is caused by a genetic defect in the γ-glutamyl cycle, affecting either glutathione synthetase or 5-oxoprolinase. While several dozens of patients with glutathione synthetase deficiency have been reported, with hemolytic anemia representing the clinical key feature, 5-oxoprolinase deficiency due to OPLAH mutations is less frequent and so far has not attracted much attention. This has prompted us to investigate the clinical phenotype as well as the underlying genotype in patients from 14 families of various ethnic backgrounds who underwent diagnostic mutation analysis following the detection of 5-oxoprolinuria. In all patients with 5-oxoprolinuria studied, bi-allelic mutations in OPLAH were indicated. An autosomal recessive mode of inheritance for 5-oxoprolinase deficiency is further supported by the identification of a single mutation in all 9/14 parent sample sets investigated (except for the father of one patient whose result suggests homozygosity), and the absence of 5-oxoprolinuria in all tested heterozygotes. It is remarkable, that all 20 mutations identified were novel and private to the respective families. Clinical features were highly variable and in several sib pairs, did not segregate with 5-oxoprolinuria. Although a pathogenic role of 5-oxoprolinase deficiency remains possible, this is not supported by our findings. Additional patient ascertainment and long-term follow-up is needed to establish the benign nature of this inborn error of metabolism. It is important that all symptomatic patients with persistently elevated levels of 5-oxoproline and no obvious explanation are investigated for the genetic etiology.