Page 51 - Read Online

Page 2 of 11 Malherbe et al. Rare Dis Orphan Drugs J 2024;3:7 https://dx.doi.org/10.20517/rdodj.2023.49

Abstract
Worldwide, comprehensive newborn screening (NBS) now includes a clinical examination at birth, hearing
screening, pulse oximetry measurement for congenital heart defects, and biochemical screening to identify
congenital disorders early in life, preventing irreversible damage, early mortality and enhancing overall health
outcomes. This article provides a comprehensive overview of biochemical NBS in South Africa, outlining the
history, current status, and future plans for NBS expansion. In South Africa, NBS is fragmented, with some
investigations included in neonatal health assessments. Historically, biochemical NBS pilot projects in the country
in the 1960s and 1980s focused on phenylketonuria and congenital hypothyroidism (CH). Despite showing initial
promise, these programmes were discontinued, largely due to competing health priorities. The current status of
biochemical NBS in South Africa is discussed, both for the state and private healthcare sectors, which collectively
screen approximately 0.5% of births annually. While recent clinical guidelines provide for a national biochemical
NBS programme, implementation has been limited, and guideline adherence remains a challenge. A brief report of a
two-day meeting held in Cape Town in February 2023 focusing on biochemical NBS for South Africa is provided.
The meeting addressed the importance of NBS, technology requirements, and the need for a comprehensive
demonstration project for biochemical CH NBS. Key challenges identified included early newborn post-delivery
discharge, technical, logistical, and infrastructure issues, as well as limited financial and human resources. Meeting
recommendations included the establishment of a National Advisory Panel for Biochemical NBS, and the
development and implementation of a demonstration project for CH biochemical NBS in two provinces.

Keywords: Biochemical newborn screening, congenital hypothyroidism, rare diseases, South Africa

INTRODUCTION
Biochemical newborn screening (NBS) is a series of tests undertaken during the first hours or days of life to
screen for congenital disorders (CDs). Some CDs, defined as abnormalities in structure or function present
from birth, are immediately obvious, while others, such as many inborn errors of metabolism (IEM) and
rare diseases, are not . By the time some conditions manifest, ranging from hours, weeks, or months after
[1,2]
birth, disease progression may already have caused irreversible damage, resulting in lifelong intellectual and
[3]
other disabilities, or premature death . This highlights the importance of early identification and referral
for treatment in asymptomatic patients before the disease manifests, to arrest disease progression.
Collectively, CDs contribute substantially to global mortality, especially more common conditions including
congenital heart defects (CHD) and haemogloinopathies, such as thalassemia and sickle cell disease
[4]
(SCD) .
Biochemical NBS began with phenylketonuria (PKU) screening using a bacterial inhibition assay developed
by Robert Guthrie, to estimate phenylalanine concentration in dried blood spots. The test was first
[8,9]
[5-7]
introduced in the USA in 1963 and then extended nationwide . Early diagnosis of PKU enables
immediate adoption of a low phenylalanine diet which minimises the accumulation of phenylalanine and
prevents seizures, stunted growth, delayed development, and irreversible intellectual disability . The
[10]
development of tests suitable for mass screening of congenital hypothyroidism (CH), congenital adrenal
hyperplasia (CAH), and cystic fibrosis (CF) followed in the late 1970s [11-13] . With the introduction of tandem
mass spectrometry (MS) in the 1990s, the number of known biochemical NBS conditions increased
rapidly [14-16] . Today, biochemical NBS is available for a multitude of treatable conditions including IEMs,
endocrine-, haemoglobin-, immune-, and other genetic disorders. The United States Recommended
Uniform Screening Panel [RUSP (https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp)]
now includes biochemical/genetic screening for a minimum of 35 core and 26 secondary conditions
(identified unintentionally when screening for core conditions), with similarly expanding panels in other