Page 61 - Read Online

Gonzaga-Jauregui et al. Rare Dis Orphan Drugs J 2024;3:16 https://dx.doi.org/10.20517/rdodj.2024.02 Page 5 of 10

Table 2. Major Mexican public healthcare providers and number of conditions that are screened for in their respective NBS/ENBS
programs
Healthcare provider Births in Mexico (%) NBS/ENBS program Number of conditions screened
PEMEX 0.2% ENBS (2005) 83 (76 IEMs, SCID, LSDs, Hemoglobinopathies)
SEDENA 0.5% ENBS > 60 conditions (IEMs, Hemoglobinopathies)
SEMAR 0.1% ENBS > 60 conditions (IEMs)
ISSSTE 2.0% ENBS (2019) 78 (IEMs)
IMSS 37% NBS 7 (CHT, CAH, PKU, BTD, GAL, CF, G6PDD)
SS 57% NBS 6 (CHT, CAH, PKU, GAL, CF, G6PDD)

NBS: Newborn screening; ENBS: expanded newborn screening; CHT: congenital hypothyroidism; PKU: phenylketonuria; CF: cystic fibrosis; GAL:
galactosemia; CAH: congenital adrenal hyperplasia; BTD: biotinidase deficiency; G6PDD: glucose-6-phosphate dehydrogenase deficiency.

fraction of newborns born at home, especially in rural areas. The approximate prevalence of 1 in
90 newborns identified with a confirmed actionable genetic inborn disorder through ENBS, highlights the
need to implement expanded newborn screening programs for early disease diagnosis and management
effectively across the country.

THE IMPORTANCE OF EARLY DIAGNOSIS
The importance of an early diagnosis to enable proper clinical and therapeutic management cannot be
overstated. Ideally, NBS/ENBS will detect a biochemical and subsequent molecular defect in the first days of
life and early enough to enable a timely intervention preventing long-term disability and mortality. A recent
report from a national tertiary medical center in Mexico showed that only 35.4% of children ascertained for
having an IEM detectable by ENBS had been screened at birth. Furthermore, these patients had an average
[13]
diagnosis time of 4 months, which is too late to intervene for many IEMs with available interventions . In
contrast, ENBS programs that can detect disorders early enough and provide appropriate management and
treatment are observing improved outcomes for patients with IEMs and LSDs .
[6,7]

Another dramatic example of the importance of early diagnosis and intervention is the recent introduction
of newborn screening for Spinal Muscular Atrophy (SMA) in some countries. The emergence of novel
molecular therapies for this condition, such as gene replacement via adeno-associated viral vectors (AAVs)
and splicing modifying molecules, has transformed the prognosis of a condition that, if untreated, results in
90% of patients being dependent on permanent mechanical ventilation or dying within the first 2 years of
life. In the last few years, three therapies have been developed and approved to treat SMA by the US Food
and Drug Administration (FDA) and the European Medicines Agency (EMA), while additional therapies
are still in development . In Mexico, the Federal Commission for Sanitary Risk Protection (Comisión
[14]
Federal para la Protección de Riesgos Sanitarios, COFEPRIS) is the approving body for new drugs and
therapeutics. The three available treatments for SMA are approved by COFEPRIS, but they are not
necessarily available to patients in the country and their cost is prohibiting for most families. Moreover, in
all cases, therapeutic success depends on the administration of the drugs at the earliest possible age and this
is only possible through early diagnosis, which can be facilitated by NBS. Among SMA patients with two
copies of the paralogue gene SMN2, 78% achieved independent walking when treated with a disease-
modifying therapy within the first 30 days of life, in comparison with 25% and 8% for those treated between
31 to 90 and after 90 days, respectively. Early intervention showed an even greater impact on motor skill
development in patients with three copies of SMN2, with 100%, 86% and 31% of children walking by
themselves when treated within the same ranges described before .
[15]