MDF Magazine Issue 64 April 2021

Doctor’s Column
Prof Amanda Krause, MBBCh, PhD MB BCh, Medical Geneticist/Associate.
Professor. Head: Division of Human Genetics. National Health Laboratory
Service (NHLS) & The University of the Witwatersrand.
Please e-mail your questions about genetic counselling to national@mdsa.
org.za.
Is newborn screening available for
muscular dystrophy?
Newborn screening aims to detect potentially fatal or disabling conditions in newborns as early as
possible, often before the infant displays any signs or symptoms of a disease or condition. Usually
multiple tests are done simultaneously using a few drops of blood from the newborn’s heel. Blood
is tested for certain genetic, endocrine, and metabolic disorders. In order to test for a condition,
there needs to be a broad, rapid test available that is relatively cheap, has a low false positive rate
and high accuracy. Newborn screening is performed in individuals where there is no family history
of a genetic condition. It is not used where there is a known family history – in these situations,
other tests should be used to test the infant for the condition known in the family. Limited newborn
screening is available to private patients in South Africa. There is no State newborn screening
programme in South Africa.
Newborn screening for muscular dystrophy has not been widespread for a number of reasons.
Firstly, there are many different conditions and thus designing a single test to detect the majority
of these is not generally possible. This may change as genetic testing develops. Further, until
recently no treatment existed to significantly alter the disease course and thus many would have
argued against screening as early diagnosis would not have made any difference. This is changing
as treatment advances.
Some countries are now screening for the commonest form of muscular dystrophy, Duchenne
(DMD), by measuring the concentration of a type of protein called CK-MM, which is part of a group
of proteins called creatine kinase. Creatine kinase is found in muscle tissue and CK-MM enters the
blood stream in increased amounts when there is muscle damage or breakdown. Elevated levels
of CK-MM detected by the kit may indicate the presence of DMD. Results showing elevated CK-
MM must be confirmed using other testing methods, such as muscle biopsies, genetic testing and
other laboratory tests. The current availability of drugs such as steroids, ataluren, eteplirsen and
golodirsen, which may significantly alter the disease course if started early, makes screening for
DMD justifiable.
Screening for spinal muscular atrophy (SMA) by genetic testing for the commonest fault worldwide
– a deletion of both copies of the SMN1 gene – has also been introduced in some countries. New
studies are suggesting that early diagnosis and initiation of treatment with drugs such as Spinraza®
(Biogen) and Zolgensma® (Novartis) achieve best outcomes when started pre-symptomatically.
What is the difference between hereditary and sporadic
inclusion body myositis?
Inclusion body myositis refers to a group of conditions which share some clinical features of
progressive muscle weakness and wasting and also have similar features on a muscle biopsy, where
so-called inclusion bodies or rimmed vacuoles are seen. Sporadic inclusion body myositis (IBM)
presents with slowly progressive distal and proximal muscle weakness, often with years between
onset of symptoms and diagnosis. It is the most common inflammatory myopathy in men older than
50. It is distinguished from inherited IBM as there is also evidence of inflammation, not present in
inherited IBM. Inherited IBM is typically a slowly progressive muscle disease that typically presents
with bilateral foot drop between ages 20 and 40 years. Affected individuals have genetic faults in
both copies of their GNE gene.
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