What is the role of lab testing in the workup of spinal muscle atrophy (SMA)?

Pru

ani

@pru A simple blood test can confirm whether the child has a mutation that causes spinal muscle atrophy (SMA; also known as spinal muscular atrophy). The SMN1 deletion test is recommended as the first diagnostic step for a patient suspected of having SMA. The deletion status can be tested by using polymerase chain reaction (PCR) to determine if both copies of SMN1 exon 7 are absent, a finding that is noted in 95% of affected individuals. PCR can reliably and accurately measure SMN1 and SMN2 copy numbers over a wide range (ie, 0-8 copies).

If the survival motor neuron (SMN) gene test is positive, the diagnosis is confirmed. However, 5% of children with the symptoms of SMA can have a negative SMN gene test and may require additional diagnostic testing. These tests can include electromyography (EMG), a nerve conduction study (NCS), or muscle biopsy and additional blood tests to help rule out other forms of muscle disease. A congenital hypotonia panel may be ordered to test for SMA. Clinical laboratories may offer panels that include tests for disorders such as SMA, myotonic dystrophy (type 1), Prader-Willi syndrome, Angelman syndrome, and maternal uniparental disomy.

In contrast to findings in patients with Duchenne muscular dystrophy and Becker muscular dystrophy, aldolase and serum creatine kinase (CK) findings are within reference ranges in patients with SMA. In later-onset SMA, these muscle enzymes may be slightly elevated.

Diagnostic delays are common in SMA. A systematic review of the literature conducted to diagnose diagnostic delay reported both age of onset and age at confirmed diagnosis; the delay to diagnosis ranged from months to years. Earlier identification of newborns with SMA will also allow infants to begin treatment even before showing symptoms, when research in human and mouse models suggests it may be most effective.