| Abstract | Klasična galaktozemija nasljedni je poremećaj metabolizma galaktoze uzrokovan manjkom galaktoza-1-fosfat-uridiltransferaze. Simptomi u novorođenačkom razdoblju razvijaju se nakon početka unosa hrane s galaktozom, a uključuju nenapredovanje, povraćanje, žuticu, ascites, koagulopatiju, kataraktu, simptome zahvaćanja mozga i bubrega te sklonost E. coli sepsi uz mogući smrtni ishod. Unatoč uspješnom zbrinjavaju početnih simptoma dijetom bez galaktoze, oboljeli često razvijaju dugoročne komplikacije poput zastoja u rastu i razvoju, osteoporozu, poremećaje govora, neurološke poremećaje i ovarijsku insuficijenciju. Dijagnostički postupak, te u nekim zemljama novorođenački probir, uključuju mjerenje galaktoze i njenih metabolita, aktivnosti galaktoza-1-fosfat-uridil-transferaze i gensku analizu. Cilj ovog rada bio je opis osobitosti bolesnika iz Hrvatske s klasičnom galaktozemijom. Ova retrospektivna studija uključila je 24 ispitanika s postavljenom dijagnozom klasične galaktozemije u razdoblju od 1977. do 2020. godine. Kao izvori podataka pregledani su bolnička arhiva, bolnički informacijski sustav i ambulantni kartoni. Dijagnoza je postavljana na temelju pozitivne obiteljske anamneze, kliničke slike, koncentracije galaktoze u krvi i urinu, a potvrđivana mjerenjem aktivnost galaktoza-1-fosfat-uridil-transferaze i analizom gena GALT. 87 % bolesnika razvilo je simptome u novorođenačkom razdoblju, a jedan bolesnik je umro. Medijan dobi pri pojavi prvih simptoma bio je četiri dana, a pri početku dijete 11,5 dana. 78,3 % bolesnika razvilo je barem jednu dugoročnu komplikaciju, uključujući poremećaje razvoja (65,2 %), ponašanja (30,4 %) i govora (52,6 %), smanjene intelektualne sposobnosti (31,6 %), neurološke komplikacije (39,1 %), kataraktu (26,1 %) i smanjenu gustoću kostiju (36,8 %). 50 % bolesnica starijih od 10 godina razvilo je ovarijsku insuficijenciju. Jasna povezanost između genotipa i fenotipa. Uspoređujući članove iste obitelji, u drugorođenih s klasičnom galaktozemijom početak dijete bio je raniji, a pojava simptoma u novorođenačkom razdoblju rjeđa, a čini se da dugoročne komplikacije nisu bile povezane s redoslijedom rođenja. Ova studija pokazuje da većina bolesnika s klasičnom galaktozemijom razvije simptome u novorođenačkom razdoblju i, unatoč strogom pridržavanju dijete, dugoročne komplikacije. |
| Abstract (english) | Classical galactosemia is an inherited disorder of galactose metabolism caused by galactose-1-phosphate-uridyltransferase deficiency. Symptoms develop after newborns become exposed to galactose-containing foods. Patients present with weight loss, vomiting, jaundice, ascites, coagulopathy, cataracts, symptoms of brain and kidney impairment and tendency for E. coli sepsis with death as a possible result. Acute manifestations are adequately controlled with a galactose-free diet, however, patients often develop long-term complications such as growth and developmental delay, speech disorders, neurological complications, osteoporosis and ovarian insufficiency. The diagnostic procedure, and in some countries neonatal screening, include the measurement of galactose and its metabolites, activity of galactose-1-phosphate-uridyl-transferase and gene analysis. The aim of this study was to describe characteristics of Croatia patients with classical galactosemia. This retrospective study included 24 patients diagnosed with classical galactosemia between 1977 and 2020. Hospital records, hospital computer database and ambulance records were reviewed as sources of data. Diagnosis was made based on positive family history, clinical presentation and galactose values in blood and urine, and confirmed by measuring galactose-1-phosphate-uridyl-transferase activity and GALT gene analysis. 87% of patients developed acute manifestations of the disease and one patient died. The median period for the onset of first symptoms was four days and for onset of therapy 11.5 days after birth. 78.3% of patients developed at least one negative long-term outcome, including developmental disorders (65.2%), behavioral disorders (30.4%), speech disorders (52.6%), impaired intellectual abilities (31.6%), neurological complications (39.1%), cataracts (26.1%) and decreased bone density (36.8%). 50% of female patients older than 10 years developed ovarian insufficiency. A clear correlation between genotype and phenotype was not detected. When comparing siblings, a galactose-free diet was started earlier in the second-born children with classical galactosemia who, consequently, had smaller incidence of symptoms in the neonatal period. However, the incidence of long-term outcomes did not appear to be connected to birth order. In conclusion, this study shows that the vast majority of patients develop symptoms in the neonatal period, as well as long-term complications despite strict adherence to a galactose-free diet. |
