Spinal muscular atrophy (SMA) is characterized by widespread muscle atrophy and flaccid paralysis. Due to degeneration of anterior horn cells in the spinal cord and motor nuclei in the brainstem, it leads to secondary peripheral nerve demyelination and muscle atrophy. This disease is inherited in an autosomal recessive manner. Linkage analysis in 80 pedigrees confirmed that SMA is linked to two DNA markers on chromosome 5q12–14, but the defective gene product remains unidentified. Based on the age of onset, it can be classified into infantile spinal muscular atrophy and juvenile spinal muscular atrophy.

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(1) Clinical Manifestations 1. Infantile Spinal Muscular Atrophy (Werdnig-Hoffmann Disease) Some cases present as an acute sexually transmitted disease. Intrauterine manifestations may include reduced fetal movement. Symptoms appear within 2 months after birth, presenting as generalized weakness and decreased limb activity. Proximal muscles of the limbs are more severely affected than distal muscles, with finger and toe movements remaining unaffected. Hypotonia is present, and tendon reflexes cannot be elicited. In the supine position, the upper and lower limbs assume a flexed and abducted posture, with the shoulders, elbows, wrists, hips, knees, and ankle joints lying flat against the bed, forming a typical frog-like posture. When the child is lifted by the chest and abdomen into a prone suspended position, the head and limbs droop, and the entire body assumes an inverted ";" shape. Due to involvement of the intercostal muscles, crying is weak, but since the diaphragm is usually unaffected, the sternum sinks during inspiration, resulting in paradoxical breathing. Facial and ocular muscles are spared, with normal facial expressions and eye movements. The condition gradually progresses, and most children die from aspiration pneumonia before the age of 1. Some cases have a later onset, occurring between 2 months and 2 years of age. Development prior to the disease is generally normal, and the child may sometimes sit independently but has difficulty standing. Limb weakness is symmetrical, more severe proximally than distally, and worse in the lower limbs than the upper limbs. Muscle atrophy is evident, and tendon reflexes are weakened or absent. In cases with longer survival, limb contractures, foot inversion, or scoliosis may develop. The disease progresses gradually, with survival possible for 10–20 years; prognosis is worse if respiratory muscles are involved. 2. Juvenile Spinal Muscular Atrophy (Juvenile Hereditary Proximal Muscular Atrophy or Kugelberg-Welander Disease) The onset is later, occurring between 2 and 17 years of age (average age 9). Early symptoms often manifest as weakness in the proximal lower limbs and pelvic girdle muscles. Delayed walking, unsteady gait, frequent falls, and difficulty standing or climbing stairs are common, resembling symptoms of muscular dystrophy. Upper limb involvement includes weakness in the shoulder girdle and upper arm muscles, but these symptoms appear later than those in the lower limbs. Significant muscle atrophy is observed in the proximal muscle groups of the lower and upper limbs, with little atrophy in the small hand muscles. Scoliosis and lordosis are often present. Contractures of the knees, hips, and ankle joints may occur. Typical cases show no cranial nerve symptoms, though a few patients may exhibit signs of motor nucleus damage. Tendon reflexes are weakened or absent, though some patients may have hyperactive reflexes. Approximately half of the patients exhibit fasciculations, which are characteristic of this disease and serve as a key distinguishing feature from muscular dystrophy. The disease progresses slowly, and patients may still be able to walk between the ages of 20 and 40. The inheritance pattern is primarily autosomal recessive, with boys more severely affected; some cases follow an autosomal dominant pattern. (2) Laboratory Findings

1. Creatine Phosphokinase (CPK): In severe infantile spinal muscular atrophy, CPK levels are mostly normal, with a few cases showing grade I elevation. Juvenile spinal muscular atrophy often exhibits grade I or grade II elevation, sometimes significantly increased.
2. Electromyography (EMG): The presence of fibrillation or fasciculation potentials is highly significant for diagnosing infantile spinal muscular atrophy. The disease typically shows prolonged motor unit potential duration, increased voltage, and potential synchronization during contraction; during strong contraction, the number of motor unit potentials decreases. The characteristic EMG changes reflect neurogenic damage, but early primary myogenic changes may dominate. The typical neurogenic pattern only appears when a sufficient number of mature anterior horn cells degenerate, so some children may not exhibit these characteristic EMG changes. Motor nerve conduction velocity is generally normal.
3. Muscle Biopsy: Striated muscle fibers show atrophy with varying thickness, nuclei clustered in chains, myofibrils loosely arranged, striations indistinct, and a reduced number of nerve fibers within the muscle. Infantile cases exhibit a positive myoglobin ATPase reaction.

bubble_chart Treatment Measures

﹝Treatment﹞

There is no specific treatment; supportive care should be strengthened, attention should be paid to preventing contracture deformities, and active measures should be taken to prevent infections. Currently, heterozygote detection or prenatal diagnosis for this disease is not possible.