SMA type 1 . (a) H&E and (b) ATPase at pH 9.4 are images from the rectus abdominis muscle biopsy performed at age of 3 months. (c) H&E of spinal cord anterior horn and (d) thoracic cord Clark column are images from the same patient at time of autopsy, at 4 months of age. Arrows in (d) indicate balloon neurons
Investigations After the Muscle Biopsy Diagnosis
The survival motor neuron (SMN) gene test showed a homozygous deletion of exons 7 and 8. The SMN2 copy number was not obtained.
Final Diagnosis
Spinal Muscular Atrophy Type 1
Patient Follow-up
The patient continued to deteriorate and his family decided to withdraw support at 4 months of age. At autopsy, the intercostal and psoas muscles showed marked neurogenic atrophy similar to the rectus abdominis muscle. Muscle from the diaphragm was relatively normal. The spinal cord showed moderate to severe loss of anterior horn pyramidal neurons and reactive astrocytosis (Fig. 31.1c). The thoracic cord Clarke neurons showed marked ballooning change in a background of reactive astrocytosis (Fig. 31.1d). Elsewhere, the lungs showed diffuse bilateral acute bronchopneumonia. Postmortem culture from the lungs grew multiple bacterial organisms including Escherichia coli, Alpha hemolytic streptococcus, Staphylococcus aureus, and Enterobacter aerogenes. The cause of death was determined as SMA type 1 complicated by failure to thrive, respiratory failure and pneumonia.
Discussion
Spinal muscular atrophy (SMA) is an autosomal recessive disease caused in 95% of cases by a homozygous deletion of exons 7 and 8 of the SMN1 gene [1] located on chromosome 5q. The most common mutation of SMN1 is a deletion of exon 7 [2]. The carrier frequency of SMN1 mutations ranges from 1 in 90 to 1 in 47 [3]. The number of SMN2 copies determines the clinical phenotype. It is classified into four types, depending on the age of symptom onset and maximal motor function achieved by the patient. SMA type 1 typically presents before 6 months of age with hypotonia, progressive proximal and distal weakness, fasciculations and the inability to achieve normal developmental milestones like head control or sitting without support [4, 5]. The intercostal muscles are affected, and the diaphragm is spared resulting in paradoxical breathing and a bell-shaped chest as seen in our patient. SMA type 2 presents between 6–18 months of age and are able to sit unassisted but are not able to achieve independent ambulation [6]. SMA type 3 presents weakness after 18 months and are able to achieve independent ambulation but in most cases will lose this ability with time. SMA type 4 usually has onset after 30 years of age. Sensation and cognition are usually spared. Differential diagnosis includes spinal muscular atrophy with respiratory distress type 1 (SMARD1) , congenital myasthenic syndromes, congenital myopathies, congenital muscular dystrophies, glycogen storage disease type II, Prader-Willi, and Zellweger as well other conditions that can present with hypotonia. Diagnosis of SMA consists of molecular genetic testing with targeted mutation analysis of the SMN1 gene and copy number analysis of the SMN2 gene . Electrophysiological studies are rarely performed.
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