Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2617_Библиотеки_им_академика_М_И_Перельмана

IMDs, a well-dened category of recently recognized and dened rare diseases, are due to mutations in genes encoding for proteins with an enzymatic or cellular transport function. They are monogenic diseases, inherited in an autosomal recessive way, or linked to the X chromosome or mitochon­drial DNA, or, more rarely, in an autosomal dominant way. Individually rare, IMDs collectively comprise more than 600 different diseases.

A detailed classication of IMDs is available at the follow­ing web address: www.ssiem.org/centralstore/ resources/ SSIEMClassicationIEM2011.pdf.

required

demand that cannot be postponed

born to be promptly included in the most appropriate thera­peutic care pathway. This is the added value of neonatal screening. The concept of the process allows a better under­standing of neonatal screening as an action of denition in each newborn of a risk condition (usually classied into three levels: low, intermediate, and high) obtained through the quantitative measurement of biological markers (single or multiple) appropriate to the condition, which must follow the diagnostic conrmation phase. The classic operational ow model of the screening process is represented in Fig.31.1, which illustrates the operational algorithm of an expanded neonatal screening program for IMD: the baseline test (amino acid and acylcarnitine analysis) is performed in all neonatal samples; if negative, it concludes the selection process; if positive (with respect to the reference interval, a statistically predened threshold value in the reference popu­lation, or a risk score calculated by dedicated computer algo­rithms), it determines actions of deepening (control), articulated according to the risk score (low, intermediate, or high risk), and conducted chronologically with a timing dened by the characteristics of the disease and the level of risk. Once this second phase has been completed, all con­rmed positives are generally reported to the clinical center of reference for diagnostic conrmation and for taking charge of the newborn at risk. This phase is carried out in concert among the screening laboratory, the laboratory for diagnostic conrmation (facilities that may coincide), and the clinical center. In any case, screening, diagnostic conr­mation, and taking charge of the newborn at risk must be concluded, even for pathologies with less severe clinical onset, within the rst month of life.

absence of screening. Additionally, the use of MS/MS tech­nology (compared to that of other technologies) can deter­mine a higher level of economic savings because of its intrinsic characteristic to detect a panel of diseases in a single test. However, previous evaluations by other authors had instead shown lower economic benets reserved for pro­grams limited in the number of diseases screened.

atic period, does not modify the natural history– inauspi-

In conclusion, it is possible to afrm that for IMDs, early postnatal diagnosis is the most effective tool for the preven­tion or reduction of both the risk of mortality and damage from severe morbidity, considering that for many rare con­genital diseases, recent years have greatly improved the approach and the possibility of therapeutic intervention. The introduction of MS/MS technology and the application of molecular biology techniques have revolutionized the neona­tal screening, allowing new scenarios of preventive medicine for IMDs.