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Nemaline myopathy (NM), first reported by Shy et al［1］ in 1963, is characterized by the presence of nemaline rods in myofibers and in the nucleus in severe cases. NM is a clinically rare, heterogeneous congenital muscle disorder, displaying dominant or recessive autosomal forms, and in rare cases, sporadic as well. Its chief manifestations are proximal muscle weakness and atrophy followed by further progress to generalized weakness and weakness of facial muscles， tongue muscles and throat muscles. Below is the case of an adult onset nemaline myopathy.
CASE
A male patient, aged 34, sought medical assistance for a neuromuscular disorder. He complained of progressive proximal muscle weakness and difficulty in walking over the 10 months previous to the hospital visit. Six months after onset, he was unable to lift his arms above his head. Eight months later, he could not get up from a chair. Later on, the patient experienced occasional difficulty in swallowing solid foods, but did not choke when drinking. His body weight decreased 10 kg in association with visible muscle atrophy of his upper and lower extremities. He displayed no fever or muscular pain and his mental function appeared normal. Clinical examination revealed that the patient had no family history of neuromuscular disease, no history of special diseases or any accident-related traumas. The patient exhibited a duck gait and generalized weakness, more prominent in proximal muscle groups (grade 2/5) than in distal ones (grade 5-/5). Other symptoms included facial muscle atrophy, difficulty in closing the mouth and eyes, decreased bilateral soft palate mobility, and absence of pharyngeal reflex. There was no atrophy of the bilateral sternocleidomastoid muscles. His reflexes were satisfactory, except for the decreased reflexes of deep tendons; otherwise, his sensory system was normal.
Numerous laboratory tests, including aldolase, creatine kinase, C-reactive protein, immunoglobulin, erythrocyte sedimentation rate, antinuclear antibodies, α-fetal protein, carcinoembryonic antigen and prostate antigen were normal. Fundus oculi, electrocardiogram, chest X-ray and abdominal ultrasound were normal. Electromyogram revealed highly polyphasic motor unit potentials of increased duration and decreased amplitude in muscles in the upper and lower extremities. Nerve conduction studies were normal. A biopsy of the left deltoid muscle was performed.
Hematoxylin eosin-stained sections of the formalin-fixed, paraffin-embedded material from the left deltoid muscle biopsy revealed prominent atrophy, marked variation in muscle fiber size, increased numbers of nuclei, and some foci of chronic inflammation.
Electron microscopic examination was performed. Osmiophilic, rectangular structures with a lattice-like appearance typical of nemaline rod bodies emanated from the Z discs of affected muscle fibers ( Figs. 1 and 2 ). No other abnormalities were found.
DISCUSSION
Nemaline myopathy (NM) is a rare muscle disorder with a wide spectrum of phenotypes, including a congenital form with fetal and neonatal onset, a mild congenital form (most common) with slow or non-progressive development and a sporadic adult-onset form.［2］
Two cases (both male) of nemaline myopathy have been reported in China. One case was a patient who developed NM at the age of 74, presenting muscle weakness and pain prominent in proximal muscle groups (grade 5-/5), but not in distal muscle groups (grade 5/5), as well as atrophy in bilateral supraspinatus muscles with normal creatine kinase levels.［3］ The other patient was a 4-year-old child, whose onset of NM was at the age of 2. He developed a duck gait and weakness in proximal muscle groups of bilateral lower limbs (grade 4/5) and abnormal creatine kinase levels.［4］ Both diagnoses were finally made by muscle biopsy.
The adult onset variant is its own distinct entity. Based on reviewing case reports, its features can be summarized as the following： ① patients' age ranges from 20 to 80 y (a mean age, 45 y), but most cases occur between 30 y and 40 y; ② there is a slight male predominance; ③ most patients have no family history of neuromuscular diseases or precursory symptoms, nor any congenital development malformation; ④ most patients manifest proximal muscle weakness and muscle atrophy with slowly progressing or progressive development associated with pain in certain cases. A smaller number of patients present generalized or distal muscle weakness, and generally there is no effect on the central nervous system or mental function; ⑤ creatine kinase levels range from normal to slightly elevated and electromyography reveals a myopathic pattern of injury; ⑥ patients often do not respond to steroid therapy and respiratory failure is the most common cause of death; ⑦ muscle biopsy is the most reliable confirmation of diagnosis. Modified trichrome stain and electron microscopic examination show numerous rods in muscle fibers, most of which are in an atrophy state. The rods, which originate from the Z line and are composed of actin and α-actinin, may either be located subsarcolemmally or centrally. However, nemaline rods are not specific for nemaline myopathy; they may also be found in the joints of normal muscles and tendons. A small number of rods may be found in other neuromuscular disorders, such as muscular dystrophy, metabolic myopathies, polymyositis and progressive spinal muscular atrophy.［5］ Therefore, accurate diagnosis requires the presence of large numbers of nemaline rods in a symptomatic patient in the absence of results typically found in other myopathies.
Approximately one-half of patients with adult-onset nemaline myopathy have an identified underlying immunologic disorder, suggesting the need for immunosuppressive therapy.［6］ In this case, however, there was no evidence of altered immunity, suggesting that the immune system is only one of the pathogenetic mechanisms involved in NM.
Congenital nemaline myopathy has so far been mapped to three genetic loci, each encoding a protein component of the sarcomeric thin filament:［7］ the NEM1 locus at 1q22-23 is the TPM3 gene that encodes γ-TM (α-tropomyosin-slow), the NEM2 locus at 2q21.1-22 is the nebulin gene, and ACHA1 at 1q42 is the skeletal muscle α-actinin gene. The typical autosomal recessive form appears to be the most common one and is caused by mutations in the nebulin gene, revealing the clinical and genetic heterogeneity of nemaline myopathy, as well as the diversity of pathological features that occur in congenital myopathies due to mutations in the same gene.
In adult patients with proximal muscle weakness, especially in those with underlying immunologic disorders, a modified Gomori trichrome stain on cryostat sections with possible confirmatory electron microscopy should be performed to avoid any misdiagnosis.
REFERENCES
1. Shy GM, Engel WK, Somer JE, et al. Nemaline myopathy: a new congenital myopathy. Brain 1963;86:793.
2. Kuitunen P, Rapola J, Noponen AL, et al. Nemaline myopathy: report of four cases and review of the literature. Acta Paediatr Scand 1972;61:353-361.
3. Li YX, Wu LJ, Chen QT, et al. Adult nemaline myopathy. J Clin Neurol 1998;6:369-370.
4. Li YX, Wu LJ, Chen QT. Nemaline myopathy with spinal muscular atrophy: report of one case. Chin J Nerv Ment Dis 2001;37:231-232.
5. Nonaka I, Ishiura S, Arahata K, et al. Progression in nemaline myopathy. Acta Neuropathol 1989;78:484-491.
6. Kymberly A, Gyure MD, Richard A, et al. Adult-onset nemaline myopathy: a case report and review of the literature. Arch Pathol Lab Med 1997;121:1210-1213.
7. Gurgel GJ, Reed U, Bang ML, et al. Nebulin expression in patients with nemaline myopathy. Neuromuscul Dis 2001;11:154-162.
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