[source]
pmid = PMID:31213928
title = A novel case report of spinal muscular atrophy with progressive myoclonic epilepsy from Iran
[diagnosis]
disease_id = OMIM:159950
disease_label = Spinal muscular atrophy with progressive myoclonic epilepsy
[text]
A 15-year old female patient was attended to neurology clinic for recent onset tremor, seizure, and
weakness in limbs. She was the first offspring of a family with relative parents; she was born from
normal spontaneous delivery. The psychomotor developmental course was normal. The symptoms initiated
with a resting tremor in both hands since the fifth year of age. When she was seven years old,
new presentations such as staring episodes and myoclonus were added. The latter feature occurred
several times a day lasting for a few seconds. Myoclonus was stimulus-sensitive, sometimes activated by
volitional movement. Five years ago, head drop attacks and multiple episodes of
generalized tonic-clonic seizure (GTCS), were initiated. Also, since the 10th year of age, a
progressive limb weakness was gradually started, especially in attempting for stair-up, standing,
and hand washing.
In physical examination, the patient was cooperative and fully oriented. She had waddling gait pattern
in walking, and her Gower`s sign was positive indicating of proximal weakness.
Muscle forces were evaluated according to the medical research council muscle scale.
Neck extensor and flexor muscles obtained 3/5, and strength of proximal muscles in upper limbs
(shoulder abductors) were 2/5. This pattern was less severe in distal muscles, where elbow and hand
muscles obtained 3/5 and 4/5, respectively. In her lower extremities, the strength was 3/5 for both hip and
knee muscles; and it was again higher in distal muscles of legs (4/5). Also, a mild weakness in
facial muscles was found; while the extra-ocular muscles were spared.
Deep tendon reflexes in Biceps brachii, Triceps brachii, Brachioradialis, and Achilles were 1+ and the
patellar knee jerk was absent. Sensory exam for small and large fibers was not remarkable.
Resting tremor was present in both hands. Patient`s tongue was obviously atrophic with fasciculation movements.
Several staring attacks and myoclonus were observed during the physical examination.
Brain MRI was done, but it did not reveal any pathologic features. Laboratory blood tests including complete
blood count (CBC), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and ammonia, plus thyroid,
renal, and liver function tests were all within normal ranges. In order to further confirming disease,
the ceramidase-activity level was obtained that revealed about 30% reduction. Moreover, a muscle biopsy of
left Biceps brachii was obtained using an open technique (Figures 1 and and 2); Histo-pathological
examination confirmed a neuropathic pattern with muscle atrophy of mainly type-II fibers, with concomitant
denervation and reinnervation processes. The video EEG monitoring was performed using a standard 10–20 system
with additional electrodes and bipolar settings; no drug was administrated to induce sedation. Both sleep and
awake phases were recorded that has been presented in Figure 3. The patient had a total of frequent epileptic
events during recording, the main features were epileptic poly-myoclonus with generalized 2.5–3 Hz
irregular sharp and slow wave complexes that was accentuated during intermittent photic stimulation (IPS).
H&E stain revealed atrophic fibers of round or angular shapes that arranged in small and large groups with
hypertrophied fibers. Fascicular atrophy was seen. Nuclear clumps were noted.
In needle electromyography (EMG) and nerve conduction study (NCS), three limbs and two
cranial nerves (V, XII) were investigated. The left upper limb was preserved for performing a muscle biopsy.
After ensuring the standard temperature in tested limbs (T=37.0), compound muscle action potential (CMAP)
[for Median, Ulnar, Tibial, and Peroneal nerves], sensory nerve action potential (SNAP) [for Median and Sural nerves],
and F-waves [from Tibial, Median and Ulnar nerves] were recorded. All NCS responses were normal.
Needle-EMG demonstrated a neuropathic pattern with high amplitude and long duration motor unit action potentials (MUAPs),
associated with reduced recruitment and spontaneous potentials such as fibrillation (Fib),
positive sharp waves (PSW), and fasciculation (Fasc). These findings confirmed
a chronic denervation process with ongoing regeneration that was compatible with the category of anterior
horn cell diseases.

Afterward, the genetic study revealed a homozygous mutation on ASAH-1 gene [ (p. Thr58Met)]; According to Gene Review® database of Washington University, this mutation was a known one; also the parents` genetic study revealed a heterozygous mutation.6 Then, treatment was started; at the first line, Depakin 500 mg/TDS, Ethosuximide 250 mg/BID, and Amantadine 100 m/BID were prescribed for the patient. But she had not a good response on the follow-up visits. We added Clonazepam 1 mg/BID and Sabril 500 mg/QD to her previous medications; however, the patient did not achieve any improvement and the symptoms were progressive. Fortunately, she is alive now and still under therapeutic regimen of the recombinant enzyme.