<p>A novel case report of spinal muscular atrophy with progressive myoclonic epilepsy from Iran</p>

Abstract

Spinal muscular atrophy (SMA) is a disorder characterized by decreased motor function due to the muscle atrophy in the background of degenerated anterior horn cells and motor cells of lower cranial nerves nuclei. The most frequent form is inherited as an autosomal recessive trait resulting from mutations in the survival motor neuron gene (SMN-1). On the other hand, a rare variant of this condition, named progressive myoclonic epilepsy subtype (SMA-PME) occurs in the result of a mutation in N-acylsphingosine amidohydrolase-1 gene (ASAH-1). The latter gene is responsible for lysosomal acid-ceramidase production. SMA-PME has been characterized by a progressive muscle weakness from ages 3–7 years, accompanied by epilepsy, an intractable seizure, and sometimes sensorineural hearing loss. In this report, we have presented a 15-year old female patient with SMA-PME that was attended to neurology clinic for a new onset tremor, seizure and proximal weakness in all limbs. We identified a homozygous mutation in exon II on her ASAH-1 gene [c.173C>T (p. Thr58Met)]. Also, a modest reduction was found in ceramidase-activity. As was expected patient`s seizures did not respond to conventional therapies.

The clinical spectrum of SMA‐PME and in vitro normalization of its cellular ceramide profile

“…Additional literature reviews were performed for 24 previously reported cases with molecularly confirmed SMA‐PME. 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 Criteria for inclusion were: an isolated neurological presentation, an adequate description of the clinical phenotype, and confirmed pathogenic variants in ASAH1 . We excluded reports of cases that lacked clinical data 26 and historical reports of SMA‐PME that lacked molecular confirmation.…”

“… 4 SMA‐PME is a rare condition and, to date, a total of 24 patients from 19 families have been reported in detail in the literature with confirmed pathogenic variation in ASAH1 . 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 Reported patients commonly present with proximal weakness in mid‐childhood, followed by progressive seizures and myoclonus. 20 Mortality may result from respiratory insufficiency in early adulthood or from complications of refractory seizures.…”

“…We analyze the clinical features and relationship of genotype to phenotype in these 6 patients and the 24 previously reported. 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 We describe pathogenic nonsense, missense, or splice site variants in ASAH1 in each patient combined with biochemical verification of AC loss of function either by the detection of elevated ceramide using high performance liquid chromatography, electrospray ionization, tandem mass spectrometry (LC–ESI–MS/MS) or by AC deficiency assessed through enzyme analysis. We further show that the cellular phenotype of increased ceramide profile can be normalized by treatment with recombinant human acid ceramidase (rhAC).…”

Spinal Muscular Atrophy and Progressive Myoclonic Epilepsy: A Rare Association

“… 2 To best of our knowledge, 44 cases of SMA-PME-like clinical presentation have been reported to date and 24 of them carried ASAH1 mutation. 2 4 5 6 …”

Managing pregnancy in a spinal muscular atrophy type III patient in Indonesia: a case report

“…Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration of lower motor neurons, leading to progressive muscular atrophy, muscle weakness, and muscle paralysis. SMA is usually associated with defect of the survival motor neuron-1 ( SMN-1 ) gene, localized in 5q11.2–q13.3 [ 1 , 2 ]. Classification of SMA is based on the age of onset and maximum motor function milestone achieved: SMA type I (Werdnig–Hoffmann disease) has onset in the first month of life, with a disability to sit unsupported and needing breathing support, with a survival chance of only up to 2-years old; SMA type II has onset between 6 and 18-months old, with the best motor ability to sit alone without support; SMA type III (Kugelberg–Welander disease) has onset between 18 months and 30-years old, with the ability to stand and walk without support; and SMA type IV has adulthood onset and tends to have normal mobility with mild muscle weakness [ 3 , 4 ].…”