Kriteriji za provođenje drugostupanjskih testova u novorođenačkom probiru na homocistinuriju i nedostatak vitamina B12

master's thesis

• Title (english): Criteria for conducting second-tier tests in newborn screening for homocystinuria and vitamin B12 deficiency
• Author: Ana Begović
• Mentor: Ksenija Fumić (mentor)
• Committee member: Ksenija Fumić (predsjednik povjerenstva)
• Committee member: Desiree Coen Herak (član povjerenstva)
• Committee member: Željka Vogrinc (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2023-08-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Rijetke bolesti imaju nisku prevalenciju u populaciji, javljaju se u manje od pet pojedinaca na 10 000 osoba i većinom
se kasno dijagnosticiraju. Nasljedne metaboličke bolesti su rijetke bolesti koje nastaju kao posljedica smanjene
aktivnosti enzima, prijenosnika ili kofaktora. NBS je postupak kojim se organizirano i sustavno otkrivaju urođene
bolesti u novorođenačkoj populaciji sa svrhom njihovog pravovremenog prepoznavanja. NBS je u RH započeo 1978.,
a danas se izvodi probira na devet nasljednih metaboličkih bolesti. Testovi probira nisu dijagnostički testovi, oni
upućuju na novorođenčad koja bi mogla imati određeni metabolički poremećaj i isključuju one koji te poremećaje
vjerojatno nemaju. Laboratoriji koji provode NBS na klasičnu homocistinuriju i manjak vitamina B12 koriste različite
postupnike. Provođenje proširenog NBS-a metodom LC-MS/MS iz uzorka DBS-a podrazumijeva analizu
aminokiselina i acilkarnitina, kao primarnih biljega, derivatiziranim ili nederivatiziranim metodama. Zbog velikog
broja lažno pozitivnih rezultata nakon analize primarnih biljega C3, C2, Met i Phe na homocistinuriju i manjak
vitamina B12, neophodno je u postupnik uvrstiti i specifičnije drugostupanjske testove (tHcy, MMA). Cilj ovog rada
je priprema proširenja novorođenačkog probira u RH na navedene bolesti. U tu je svrhu napravljena usporedba
šestomjesečnih rezultata mjerenja analita od interesa (C3, C2, Met i Phe) i njihovih međusobnih omjera u NBS-u RH s
vrijednostima istih analita koji se koriste u postupnicima novorođenačkih programa Austrije, Italije, Njemačke i
Španjolske. Procijenjeno je da bi primjenom kriterija iz postupnika navedenih zemalja na rezultate NBS RH, za
šestomjesečno razdoblje, broj uzoraka za mjerenje Hcy u drugostupanjskom testu bio prihvatljiv za provođenje NBS-a
na homocistinuriju i manjak vitamina B12 u RH.

Abstract (english)

Rare diseases have a low prevalence in the population, they occur in less than five individuals per 10 000 people and
are mostly diagnosed late. Inherited metabolic diseases are rare diseases that occur as a result of reduced activity of
enzymes, transporters or cofactors. NBS is a procedure for the organized and systematic detection of congenital
diseases in the newborn population with the purpose of their timely recognition. In the Republic of Croatia NBS
started in 1978, and today screening is performed for nine inherited metabolic diseases. Screening tests are not
diagnostic tests, they indicate newborns who may have a certain metabolic disorder and exclude those who probably
do not have these disorders. Laboratories that perform NBS for classic homocystinuria and vitamin B12 deficiency
use different procedures. Carrying out an extended NBS using the LC-MS/MS method from a DBS sample implies the
analysis of amino acids and acylcarnitine, as primary markers, by derivatized or non-derivatized methods. Due to the
large number of false positive results after the analysis of the primary markers C3, C2, Met and Phe for
homocystinuria and vitamin B12 deficiency, it is necessary to include more specific second-tier tests (tHcy, MMA) in
the procedure. The aim of this paper is to prepare the extension of newborn screening in Croatia for the mentioned
diseases. For this purpose, a comparison was made of the six-month results of measuring the analytes of interest (C3,
C2, Met and Phe) and their mutual ratios in the NBS of the Croatia with the values of the same analytes used in the
procedures of the newborn programs of Austria, Italy, Germany and Spain. It was estimated that by applying the
criteria from the procedures of the mentioned countries to the results of the NBS of the Republic of Croatia, for a
six-month period, the number of samples for measuring Hcy in the second-tier test would be acceptable for conducting
the NBS for homocystinuria and vitamin B12 deficiency in Croatia.

• Keywords: novorođenački probir; drugostupanjski testovi; homocistinurija; vitamin B12
• Keywords (english): newbornscreening; decond-tier test; homocystinuria; Vitamin B12
• Language: croatian
• URN:NBN: urn:nbn:hr:163:793745
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-11-21 13:41:40