Case reportConcurrent positive anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase antibody with reducing body myopathy: Possible double trouble
Introduction
Immune mediated necrotizing myopathy (IMNM), a recently recognized but a common entity among the heterogenous group of inflammatory myopathies, has been classified by the ENMC Immune-Mediated Necrotizing Myopathies Working Group into (1) anti-signal recognition particle (anti-SRP) positive IMNM or anti-SRP myopathy, (2) anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) positive IMNM or anti-HMGCR myopathy, and (3) antibody negative IMNM using integrated clinical, serological, and pathological criteria [1]. Patients with proximal muscle weakness and elevated serum creatine kinase (CK) level can be classified into anti-SRP myopathy or anti-HMGCR myopathy if they are found to have anti-SRP or anti-HMGCR antibody, respectively [1]. Further workup such as muscle biopsy, electromyography (EMG), and muscle magnetic resonance imaging (MRI) is not required for subtyping these seropositive patients [1]. In contrast, compatible muscle pathology is essential to define antibody negative IMNM in patients with similar clinical features after excluding possibility of drug/toxin-induced myopathy [1]. Although most IMNM patients are adults, pediatric IMNM exists and is probably underrecognized. It is noteworthy that IMNM can be masquerading as muscular dystrophy and vice versa especially in pediatric individuals [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. Instead of acute or subacute clinical presentation and necrotic and regenerating process on pathology, some IMNM patients show indolent clinical course and chronic or advance muscle pathology mimicking muscular dystrophy [3], [4], [6], [12]. On the other hand, certain types of muscular dystrophies including anoctaminopathy, laminopathy, dysferlinopathy, sarcoglycanopathies, FKRP-related muscular dystrophy and fascioscapulohumeral muscular dystrophy (FSHD) can be pathologically deceptive as IMNM by showing prominent necrotic and regenerating process with lymphohistiocytic inflammation [1], [3]. Interestingly, some of muscular dystrophy patients may show favorable response to immunotherapies [3]. Thorough clinical, laboratory, and genetic investigations are required to distinguish potentially treatable conditions, IMNM, from other non-treatable conditions.
Here, we report a case of a 6-year-old boy who has concurrent positive anti-HMGCR antibody and reducing body myopathy (RBM) emphasizing the possibility of co-occurrence of IMNM and muscular dystrophy and importance of comprehensive workup in cases with unusual presentations.
Section snippets
Case report
The patient was a 6-year-old Thai boy from a non-consanguineous family, who had presented with proximal muscle weakness for 18 months. His parents first noticed the symptoms after the patient recovered from chickenpox when he was 4 years and 6 months old. At 5 years of age, he had difficulties getting upstairs, rising from the floor, frequent falling, and walking tiptoe. At the age of 6, the patient could not walk up and down stairs and had difficulties raising his arms. The patient had
Discussion
Several cases of concurrent myositis specific autoantibody (MSA) positivity with different types of muscular dystrophy/myopathy have been reported in the literature including positive anti-HMGCR antibody with reported ANO5 [16] and LMNA [3] mutations, positive anti-SRP antibody with COL6A3 variant [5], positive anti-Jo-1 antibody with genetically confirmed, muscular dystrophy (LGMD) 2A [11], positive anti-Mi2 antibody with mitochondrial myopathy [17] and genetically confirmed FSHD [11] (Table 1
Acknowledgments
This study was supported partly by Intramural Research Grant (29–4) for Neurological and Psychiatric Disorders of NCNP, and AMED under Grant Numbers JP19ek0109285h0003 and JP18kk0205001s0203.
Conflict of interest
Dr. Lundberg has filed a patent for anti-FHL1 antibody test. The other authors do not have conflict of interest to declare.
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2021, Clinical Neurology and NeurosurgeryCitation Excerpt :Unlike most previously reported pediatric myopathies associated with HMGCR antibodies, this child showed little response to immunotherapies [5]. Muscle biopsy showed reducing bodies, in addition to changes suggestive of myofiber necrosis and regeneration [5]. The diagnosis of RBM was confirmed by a reported c.368A>G (p.His123Arg) mutation in the FHL1 gene, the same variant present in our patient [5].
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2020, Neuromuscular DisordersCitation Excerpt :Reports on pediatric patients with anti-HMGCR myopathy are relatively recent and infrequent. In a systematic literature review, we found 39 children reported with anti-HMGCR myopathy; three small pediatric series [9,10,19], three single cases [11,20,21], and five larger primarily adult series [2–4, 22,23] (Table 2 Suppl.). The percentage of positive anti-HMGCR antibody in the three different series of pediatric patients with different types of inflammatory myopathies ranged between 1% and 15%.
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