SMA Diagnostics

How does the diagnostics for 5q-Spinal Muscular Atrophy (SMA) work?

Testing Algorithm for 5q-Spinal Muscular Atrophy

Our service is ideal for identification of SMA in at-risk patients showing specific clinical symptoms or for an individual or family member who has a family history of SMA.

We provide a SMA Sampling Kit which includes:

  • Dried Blood Spot card (DBS)
  • Informed Consent Form (ICF)
  • Envelope for the return of the Sampling Kit (including ICF and DBS card) to ARCHIMEDlife Laboratories
  • Instructions for Blood Sampling and Shipment

After sample collection is complete, please return the Sampling Kit (including the DBS card and ICF) to ARCHIMEDlife Medical Laboratories using the shipping instructions provided. Diagnostic results will be available within a few working days.

The diagnostic algorithm

How results are reported

Primary diagnostics for 5q-SMA involves the determination of SMN1 gene copy number in adults or infants suspected of 5q-SMA. Our diagnostics can result in one of three possible findings.

Medical report 1


Result: No SMN1 gene copy was determined.

Interpretation: Spinal Muscular Atrophy (SMA) is confirmed.

ARCHIMEDlife laboratory will proceed with SMN2 copy number analysis. 

Medical report 2


Result: One SMN1 gene copy was determined.
ARCHIMEDlife laboratory will proceed with sequence analysis.

(a) SMN1 mutation was detected.

Interpretation: Spinal muscular atrophy (SMA) is confirmed.
Our laboratory proceeds with SMN2 copy number analysis (see Step 2). A dried blood spots (DBS) card of family members may be required for confirmatory testing.

 

(b) No SMN1 mutation was detected.

Interpretation: Carrier status of spinal muscular atrophy (SMA) is confirmed. The affected infant/adult has one normal copy of SMN1 gene.

Medical report 3


Result: Two or more SMN1 gene copies were determined.
Interpretation: 5q-spinal muscular atrophy (SMA) could not be confirmed. Please consider other diseases.

Differentialdiagnose bei muskulärer Hypotonie

Disorders
Manifestation < 6. months of life		 Gene(s) or region inheritance Differentiates from SMA
Pompe disease

(Glycogen storage disease II)

 17q25.2-25.3
GAA		 AR hypertrophic cardiomegaly
X-linked infantile spinal muscular atrophy Xp11.3
UBA1		 XR arthrogryposis
Spinal muscular atrophy with respiratory distress 1 (SMARD1) 11q13.3
IGHMBP2		 AR predominant upper limb
distal muscular weakness
diaphragmatic paralysis
Prader-Willi-syndrome 15q11.2-q13
NDN, SNRPN		 AD floppy infant
mental retardation
craniofacial features
Myotonic dystrophy type 1
(Curschmann-Steinert syndrome)		 19q13.2-13.3
DMPK		 AD initial distal muscular weakness
eye involvement
Congenital muscular dystrophy 6q22.33
LAMA2		 AR brain abnormalities, seizures ophthalmoplegia
Peroxisome biogenesis disorders (Zellweger spectrum) many genes
PEX		 AR renal cysts
hepatosplenomegaly
Congenital myasthenic syndrome many genes AR, AD ophthalmoplegia, ptosis
respiratory insufficiency
Other: congenital myopathies, metabolic/mitochondrial myopathies, peripheral neuropathies
Manifestation > 6. months of life
Botulism – – acute onset
cranial nerve palsy
Polyneuropathy
(Guillain-Barré syndrome)		 17p12
PMP22		 AD? subacute onset
sensory involvement
Duchenne muscular dystrophy Xp21.2-p21.1
DMD		 XR cardiomyopathy
respiratory insufficiency
Hexosaminidase A deficiency
(Tay-Sachs disease)		 15q23
HEXA		 AR spinocerebellar degeneration
macula pallor (cherry red spot)
Progressive bulbar palsy
(Fazio-Londe disease , Riboflavin transporter deficiency)		 20p13
SLC52A2
SLC52A3		 AR cranial nerve paralysis
progressive bulbar palsy
dysphagia
Monomelic amyotrophy (Hirayama disease) – – regards distal, upper limb
Juvenile amyotrophic lateral sclerosis
(ALS 5)		 15q21.1
SPG11		 AR distal muscular weakness
Spinal and bulbar muscular atrophy of Kennedy Xq12
AR		 XR bulbar muscular weakness
weakness of facial muscles
Spinal muscular atrophy late onset (Finkel type) 20q13.32
VAPB		 AD onset > 30 years
Other: peripheral neuropathies, muscular dystrophies

 

Table 1.

Frequent differential diagnosis of muscular hypotonia (list is not complete).
XR; X-linked recessive, AR; autosomal recessive, AD; autosomal dominant