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Introduction: Recessive mutations in the gene encoding the histidine triad nucleotide-binding protein 1 (HINT1) are associated with axonal motor-predominant Charcot-Marie-Tooth (CMT) disease with neuromyotonia. A total of 24 HINT1 gene mutations have been reported so far. Some of these cases had mild to moderate elevations of creatinine kinase with no earlier reports of muscle biopsy findings in these cases. In this study, we describe a patient with axonal motor-predominant neuropathy and myopathy with rimmed vacuoles, likely due to a novel HINT1 gene mutation. Case report: A 35-year-old African American man presented with insidious onset and progressive symmetric distal leg weakness followed by hand muscle atrophy and weakness since the age of 25. He had no muscle cramps or sensory complaints. His 38-year-old brother developed similar symptoms beginning in his early 30 s. On neurologic examination, the patient had distal weakness and atrophy in all limbs, claw hands, pes cavus, absent Achilles reflexes, and normal sensory examination. Electrodiagnostic studies revealed absent/reduced compound motor action potential amplitudes distally with normal sensory responses with no neuromyotonia. His sural nerve biopsy showed a chronic non-specific axonal neuropathy, and a biopsy of the tibialis anterior muscle demonstrated myopathic features and several muscle fibers harboring rimmed vacuoles without inflammation in addition to chronic denervation changes. A homozygous variant, p.I63N (c.188T > A), in the HINT1 gene was found in both brothers. Conclusion: We describe a novel, likely pathogenic, HINT1 pI63N (c.188T > A) homozygous variant associated with hereditary axonal motor-predominant neuropathy without neuromyotonia in two African American brothers. The presence of rimmed vacuoles on muscle biopsy raises the possibility that mutations in the HINT1 gene may also cause myopathy.
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Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.
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Dermatite Fototóxica , Doenças Genéticas Ligadas ao Cromossomo X , Hepatopatias , Guias de Prática Clínica como Assunto , Protoporfiria Eritropoética , Humanos , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Protoporfiria Eritropoética/diagnóstico , Protoporfiria Eritropoética/genética , Protoporfiria Eritropoética/terapiaRESUMO
Acute hepatic porphyrias (AHPs) typically present with recurrent acute attacks of severe abdominal pain and acute autonomic dysfunction. While chronic symptoms were historically overlooked in the literature, recent studies have reported increased prevalence of chronic, mainly neuropathic, pain between the attacks. Here we characterize acute and chronic pain as prominent manifestations of the AHPs and discuss their pathophysiology and updated management. In addition to the severe abdominal pain, patients could experience low back pain, limb pain, and headache during acute attacks. Chronic pain between the attacks is typically neuropathic and reported mainly by patients who undergo recurrent attacks. While the acute abdominal pain during attacks is likely mediated by autonomic neuropathy, chronic pain likely represents delayed recovery of the acute neuropathy with ongoing small fiber neuropathy in addition to peripheral and/or central sensitization. δ-aminolaevulinic acid (ALA) plays a major role in acute and chronic pain via its neurotoxic effect, especially where the blood-nerve barrier is less restrictive or absent i.e., the autonomic ganglia, nerve roots, and free nerve endings. For earlier diagnosis, we recommend testing a spot urine porphobilinogen (PBG) analysis in any patient with recurrent severe acute abdominal pain with no obvious explanation, especially if associated with neuropathic pain, hyponatremia, autonomic dysfunction, or encephalopathy. Of note, it is mandatory to exclude AHPs in any acute painful neuropathy. Between the attacks, diagnostic testing for AHPs should be considered for patients with a past medical history of acute/subacute neuropathy, frequent emergency room visits with abdominal pain, and behavioral changes. Pain during the attacks should be treated with opiates combined with hemin infusions. Symptomatic treatment of chronic pain should start with gabapentinoids and certain antidepressants before opiates. Givosiran reduces levels of ALA and PBG and likely has long-term benefits for chronic pain, especially if started early during the course of the disease.
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Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.
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COVID-19 , Intolerância Ortostática , Síndrome da Taquicardia Postural Ortostática , COVID-19/complicações , Progressão da Doença , Fadiga/complicações , Humanos , Intolerância Ortostática/complicações , Intolerância Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/complicações , Síndrome da Taquicardia Postural Ortostática/diagnóstico , SARS-CoV-2RESUMO
Orthostatic intolerance (OI) following pediatric concussion is not well understood. Assessing the prevalence of concussion-related OI and how it compares to non-concussion-related OI will improve care for patients suffering with these symptoms. OBJECTIVE: We set out to describe concussion-related OI in adolescence, with particular emphasis on time to recovery and differences from non-concussion-related OI (including male vs. female prevalence). Retrospective chart reviews were completed on post-concussion patients endorsing symptoms of OI. The patients' sex, sport history, previous concussions, time since injury, and recovery time were analyzed and compared between males and females as well as against general OI statistics. Thirty-nine pediatric patients, representing 8.7% of all new patients referred to a specialized concussion clinic over a 13-month interval, were included in the chart review. Mean age of onset was 15.0 ± 2.5 years and 18 (46%) were males. The median times from evaluation to symptom resolution were 120 days. Of 18 patients who completed head-up tilt table testing, 17 (94%) had orthostatic tachycardic response (>40 bpm heart rate increment). Post-concussive OI differs from other orthostatic intolerance etiologies, lacking a strong female predominance and exhibiting a shorter time course to recovery compared to other etiologies of OI (but longer recovery time compared to concussion patients in general). Clinical orthostatic vital signs may not be sensitive for diagnosing orthostatic intolerance in athletes, likely due to higher vagal tone and more efficient skeletal muscle pump.
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Concussão Encefálica , Intolerância Ortostática , Adolescente , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Criança , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Intolerância Ortostática/diagnóstico , Intolerância Ortostática/epidemiologia , Intolerância Ortostática/etiologia , Estudos Retrospectivos , Teste da Mesa Inclinada/efeitos adversosRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.
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Esclerose Lateral Amiotrófica/sangue , Biomarcadores/sangue , Fatores de Crescimento de Fibroblastos/sangue , Regulação da Expressão Gênica , Músculo Esquelético/metabolismo , Superóxido Dismutase-1/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/metabolismo , Animais , Biomarcadores/metabolismo , Biópsia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Superóxido Dismutase-1/metabolismo , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND/OBJECTIVE: Weight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients to explore its utility as a biomarker of disease progression. METHODS: DEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). RESULTS: The ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8). CONCLUSION: Measurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.
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Tecido Adiposo/patologia , Esclerose Lateral Amiotrófica/patologia , Absorciometria de Fóton , Tecido Adiposo/diagnóstico por imagem , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Biomarcadores , Índice de Massa Corporal , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.
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Neuropatias Diabéticas/diagnóstico , Síndrome Metabólica/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Cirurgia Bariátrica , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Dietoterapia , Progressão da Doença , Dislipidemias/epidemiologia , Dislipidemias/metabolismo , Dislipidemias/terapia , Exercício Físico , Humanos , Hipoglicemiantes/uso terapêutico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/terapia , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/terapia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/terapia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/metabolismo , Fatores de Risco , Neuropatia de Pequenas Fibras/diagnóstico , Neuropatia de Pequenas Fibras/epidemiologia , Neuropatia de Pequenas Fibras/fisiopatologia , Neuropatia de Pequenas Fibras/terapia , Topiramato/uso terapêuticoRESUMO
BACKGROUND: The extrapolated reference values procedure (E-Ref) was used to compare data from a single institution with the recently published reference value (RV) for concentric electrode jitter. METHODS: Data from voluntarily activated concentric needle jitter studies in the frontalis muscle were obtained using retrospective chart review. All measured signals were reviewed for acceptable quality. Cutoff values for increased jitter were calculated using E-Ref, and compared with the published RVs. RESULTS: At total of 1501 apparent single-fiber action potential (ASFAP) pairs were reviewed; 1371 ASFAP pairs were determined to have acceptable quality. The cutoff value identified by E-Ref from all reviewed ASFAP pairs was 36 microseconds and the cutoff for acceptable pairs was 35 microseconds. Using either of these cutoff values (36 or 35 microseconds) did not result in a significant difference in percentage of jitter recordings considered normal when compared with the recently published RV (38 microseconds). DISCUSSION: The single-institution jitter cutoff value obtained by E-Ref gives results that are not significantly different from the reported RV.
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Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Junção Neuromuscular/fisiologia , Potenciais de Ação/fisiologia , Adulto , Eletrodos , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos RetrospectivosRESUMO
Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-ß, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed ß-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.
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Esclerose Lateral Amiotrófica/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neurônios Motores/patologia , Denervação Muscular , Músculo Esquelético/patologia , Atrofia Muscular/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Neurônios Motores/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Adulto JovemRESUMO
PURPOSE OF REVIEW: To review the peripheral neurological complications of the acute hepatic porphyrias, as well as the latest advances in their pathophysiology and management. RECENT FINDINGS: The diagnosis of porphyric neuropathy remains challenging as varying neuropathic patterns are encountered depending on disease stage, including a non-length-dependent distribution pattern. The major pathophysiologic mechanism is δ-aminolevulinic acid (ALA)-induced neurotoxicity. The less restrictive blood-nerve barrier in the autonomic ganglia and myenteric plexus may explain the frequency of dysautonomic manifestations. Recently, a prophylactic small interfering RNA (siRNA)-based therapy that reduces hepatic ALA Synthase-1 mRNA was approved for patients with recurrent neuro-visceral attacks. Neurologists should appreciate the varying patterns of porphyric neuropathy. As with most toxin-induced axonopathies, long-term outcomes depend on early diagnosis and treatment. While the short-term clinical and biochemical benefits of siRNA-based therapy are known, its long-term effects on motor recovery, chronic pain, and dysautonomic manifestations are yet to be determined.
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Doenças do Sistema Nervoso Periférico , Polineuropatias , Porfirias Hepáticas , Humanos , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Sintase do PorfobilinogênioRESUMO
Extra-renal expression of Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) has been well recognized and reflects the importance of intracrine/paracrine vitamin D signaling in different tissues under physiological and pathological conditions. In a prior RNA sequencing project, we identified CYP27B1 mRNA as upregulated in muscle samples from patients with amyotrophic lateral sclerosis (ALS) compared to normal controls. Our aims here were: (1) to validate this finding in a larger sample set including disease controls, (2) to determine which cell type is expressing CYP27B1 protein in muscle tissue, (3) to correlate CYP27B1 mRNA expression with disease progression in the SOD1G93A ALS mouse and in ALS patients. We assessed CYP27B1 expression by qPCR, western blot, and immunohistochemistry in a repository of muscle samples from ALS, disease controls (myopathy and non-ALS neuropathic disease), normal subjects, and muscle samples from the SOD1G93A mouse. Eight ALS patients were studied prospectively over 6-12 months with serial muscle biopsies. We found that CYP27B1 mRNA and protein levels were significantly increased in ALS versus normal and myopathy muscle samples. Neuropathy samples had increased CYP27B1 mRNA and protein expression but at a lower level than the ALS group. Immunohistochemistry showed that CYP27B1 localized to myofibers, especially those with features of denervation. In the SOD1G93A mouse, CYP27B1 mRNA and protein were detected in skeletal muscle in early pre-symptomatic stages and increased through end-stage. In the human study, increases in CYP27B1 mRNA in muscle biopsies correlated with disease progression rates over the same time period. In summary, we show for the first time that CYP27B1 mRNA and protein expression are elevated in muscle fibers in denervating disease, especially ALS, where mRNA levels can potentially serve as a surrogate marker for tracking disease progression. Its upregulation may reflect a local perturbation of vitamin D signaling, and further characterization of this pathway may provide insight into underlying molecular processes linked to muscle denervation.
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25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Músculo Esquelético/metabolismo , Adulto , Idoso , Animais , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Regulação para Cima , Vitamina D/metabolismoRESUMO
Hereditary transthyretin amyloidosis, once a rare progressive neuropathy and/or cardiomyopathy, is now recognized with increasing worldwide frequency, various phenotypes, and over 130 gene mutations identified to date. This inherited disorder develops as a result of mutated transthyretin amyloid aggregation and systematic deposition throughout the body. With increasing knowledge about the pathophysiology of this disease, new disease-modifying therapies are being developed. In addition to slowing progression, these new agents were found to improve quality of life and reduce the severity of neuropathic symptoms. Two new gene-modifying therapies recently received Food and Drug Administration approval following the positive results from phase III trials. These include an antisense oligonucleotide, inotersen, and small interfering RNA, patisiran, which were reported to reduce the production of transthyretin and had promising safety profiles. Additional novel therapies are being explored with hopes to prolong survival. Therefore, early diagnosis of this treatable disorder has become increasingly important in clinical practice.
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Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/fisiopatologia , Neuropatias Amiloides Familiares/terapia , HumanosRESUMO
PURPOSE OF REVIEW: Hereditary sensory and autonomic neuropathies (HSANs) are a clinically heterogeneous group of inherited neuropathies featuring prominent sensory and autonomic involvement. Classification of HSAN is based on mode of inheritance, genetic mutation, and phenotype. In this review, we discuss the recent additions to this classification and the important updates on management with a special focus on the recently investigated disease-modifying agents. RECENT FINDINGS: In this past decade, three more HSAN types were added to the classification creating even more diversity in the genotype-phenotype. Clinical trials are underway for disease-modifying and symptomatic therapeutics, targeting mainly HSAN type III. Obtaining genetic testing leads to accurate diagnosis and guides focused management in the setting of such a diverse and continuously growing phenotype. It also increases the wealth of knowledge on HSAN pathophysiologies which paves the way toward development of targeted genetic treatments in the era of precision medicine.
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Neuropatias Hereditárias Sensoriais e Autônomas/classificação , Humanos , Mutação , FenótipoRESUMO
Multiminicore disease is a myopathy that is pathologically characterized by the presence of multiple areas of small, short, and poorly delineated zones of sarcomeric disorganization lacking mitochondria (minicores) that can be observed in both type 1 and type 2 fibers. Most cases of multiminicore disease typically present with early-onset axial weakness, respiratory insufficiency, scoliosis, and rigid spine. There is no correlation between the frequency of minicores and clinical severity. Multiminicore disease is genetically heterogeneous and can result from recessive or dominant mutations. Genetic testing is needed to establish the precise diagnosis and provide overall prognosis. Here we report a 23-year-old woman with respiratory failure, distal joint hyper-laxity, scoliosis and rigid spine due to multiminicore disease caused by a novel compound heterozygous mutation in the selenoprotein N1-encoding gene (SELN). The preserved ambulation into adulthood and normal creatinine kinase (CK) favor the diagnosis of congenital myopathy over congenital muscular dystrophy (CMD). However, the nonspecific myopathic histopathological changes and extremely rare minicore-like structures can make it challenging to differentiate between SELN-myopathy and congenital muscular dystrophies, such as Ullrich or lamin A/C-CMD.
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Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/genética , Oftalmoplegia/diagnóstico , Oftalmoplegia/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/deficiência , Selenoproteínas/genética , Feminino , Humanos , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/patologia , Mutação , Mutação de Sentido Incorreto , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adulto JovemRESUMO
OBJECTIVE: To evaluate the associated diseases, polyneuropathy correlates, and risk covariates of neuropathic plantar ulcers (PUs) and neuropathic arthropathies (NAs). DESIGN: The authors conducted a retrospective, observational study over 3.5 years of 69 patients with neuropathy, NA, or PU seen in a wound clinic who also had a comprehensive neurologic evaluation and neurophysiologic testing. Comparisons were made to a population representative cohort of patients with diabetes mellitus (DM; n = 259). RESULTS: Of the 69 wound clinic patients, 32 had PUs, 14 had NAs, and 23 had both. Of the 61 adequately assessed patients, 37 (61%) had DM, 22 (36%) had no known associated disease, and 2 (3%) had hereditary sensory and autonomic neuropathy. Of the 37 patients with DM, 35 had distal polyneuropathy, and 2 did not. In 22 patients with chronic idiopathic axonal polyneuropathy, 20 had distal polyneuropathy. CONCLUSIONS: Although DM was the disease most commonly associated with PUs and NAs, chronic hyperglycemia may not have been the major underlying risk factor. The major risk covariates are sensation loss from polyneuropathy, old age, obesity, repetitive foot injury, and inadequate foot care or treatment. Physicians and other healthcare providers can help by identifying patients at risk and instituting measures such as adequate foot care to decrease these risks.