The diagnosis of Werdnig-Hoffmann
disease is confirmed by DNA study. The genetic abnormality is at the 5q
Neonates with the clinical findings of Werdnig-Hoffmann disease and a
negative DNA study should undergo EMG, nerve conduction, tensilon trial,
and muscle biopsy to exclude the possibility of other causes of hypotonia
with decreased dynamic tone. The EMG of a neonate with Werdnig-Hoffmann
disease shows fibrillation potentials. Fasciculations are rare.
Occasionally a peculiar pattern of spontaneous bicouple discharges may
be present. Muscle biopsy may show panfascicular atrophy and type I fiber
hypertrophy. The loss of checkerboard appearance and the presence of type
grouping that is characteristic of Werdnig-Hoffmann disease during childhood
is not present in most neonates with Werdnig-Hoffmann disease. The only
treatment for neonates with Werdnig-Hoffmann disease is supportive.
Muscular Atrophy with Respiratory Distress Type 1
with Spinal Muscular Atrophy with Respiratory Distress Type 1 look the
same as neonates with Spinal Muscular Atrophy (Werdnig-Hoffmann disease).
The features that distinguish spinal muscular atrophy respiratory distress
type 1 are diaphragmatic weakness, distal limb wasting, distal arthrogryposis
and bulky proximal fingers (Figure 32.1). Diaphragmatic weakness may lead
to apnea and respiratory distress. Spinal Muscular Atrophy with Respiratory
Distress Type 1 is due to a mutation in the gene encoding inmunoglobulin
mu-binding protein 2. This gene is located on chromosome 11.
Figure 132.1.— [A] The bulky proximal digits (prominent fat
pad) contrast with the wasted appearance of more distal regions of the
fingers. [B] Right diaphragmatic paralysis.
disease or acid maltase deficiency occurs less frequently than Werdnig-Hoffmann
disease. The gene locus is at the 17q 23-25 site. Pompe disease is an
autosomal recessive disorder caused by alpha-glucosidase deficiency.
Alpha-glucosidase deficiency leads to increased glycogen deposition in
lysosomes of many different tissues, including the anterior horn motor
neurons and muscle. The most common clinical manifestations are hypotonia
with decreased dynamic tone (without the typical distribution of Werdnig-Hoffmann
disease), congestive heart failure, a large tongue, bulky muscles, and
a firm liver. The deposition of glycogen in the cardiac muscle lysosomes
leads to a large heart with shortened PR intervals, elevated R-waves,
and inverted T-waves. Muscle biopsy reveals large amounts of periodic
acid Schiff (PAS)-positive material. The enzymatic defect can be demonstrated
in leukocytes and fibroblasts. Prenatal diagnosis from amniotic fluid
fibroblasts is possible.
There is no specific treatment. Death due to cardiac failure often occurs
at a young age.