Proximal Muscle Wasting Research Articles

A - 45 Duchenne and Becker Muscular Dystrophy: Sibling Case Studies

Abstract Objective Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular condition primarily affecting males. Progressive proximal muscle wasting and weakness is seen and a shortened life span can occur due to cardiac involvement. Becker Muscular Dystrophy (BMD) is a milder form of DMD. Non-progressive cognitive impairment (e.g., lower IQ) in DMD has been well established, while the cognitive profile in BMD is less known. DMD/BMD are caused by mutations in the dystrophin protein. Research suggests that mutations downstream of exon 63 in the DMD gene are associated with poorer cognitive outcomes compared to upstream 1–30. Our cases explore the association between genetic/medical factors upon cognitive and behavioral outcomes, and neuropsychological similarities/differences between DMD and BMD. Method The current sibling case studies include one BMD set (mutations at exon 45–49) and two DMD sets (exon 61–74, and 13, respectively). They are part of a larger IRB-approved research dataset. Notably in DMD set two, the siblings have different biological fathers. Results The BMD siblings have comparable neuropsychological profiles (e.g., below average IQ, academic challenges, attention/executive problems). In DMD set one, one sibling has average intelligence with no academic challenges, while the other sibling has a low average IQ with challenges in math and spelling. In DMD set two, one sibling has intact cognitive functioning, while the other sibling performs well below average across neurocognitive domains. Conclusions Our results indicate variabilities in DMD/BMD, highlighting the contributing role of established factors (e.g., mutation location) and additional non-DMD influences (e.g., genetic contributions from biological father) to understand neuropsychological profiles.

FRI634 Diagnostic Delay Of Diabetic Amyotrophy Is Associated With Complicated Disease Leading To Mental, Physical, And Financial Debilitation- A Case Report

Abstract Disclosure: A.J. Zaidi: None. W. Staehle: None. Introduction: Delay in diagnosis is a major problem impacting medicine, especially if pathology is not very common, like Diabetic amyotrophy. It typically presents with unilateral proximal muscle weakness and pain affecting thighs, hips and buttocks. It is relatively a rare neurological complication of Diabetes Mellitus and prediabetes, affecting approximately 1 percent of the patients. It is commonly underrecognized leading to long course to diagnosis. Case presentation: A 58 year old female presented to clinic with 5 year history of Lower back and left hip pain, slowly progressive leg weakness, with weight loss 25 pounds. Her past medical history included Type 2 diabetes mellitus with A1C 6.9, controlled by Metformin alone. She had multiple previous presentations to local primary care physicians, with unclear clinical diagnosis. She underwent several tests and imaging, was seen by neurologist, orthopedist and spine physician. Her treatments included pain regimens with N-acetylcysteine, Ibuprofen, gabapentin, tizanidine, lidocaine patch, low dose steroids, physical therapy and chiropractor visits. These provided only partial symptomatic relief. She had no other significant history, She lost her job due to being limited by her pain. Exam revealed discomfort to palpation on lower lumbar, generalized atrophy of left thigh muscles, asymmetric proximal weakness, normal sensation and reflexes. Blood work showed normal ESR, CRP, CPK, ANA, myomarker panel, Vit D levels. CSF evaluation was deferred by the patient. Imaging from previous records included Hip X-ray with mild degenerative disease, Lumbar CT with mild arthropathy on the Left L5- S1. Unremarkable lumbar and Sacral MRI. EMG revealed L4 radiculopathy with denervation of L vastus medialis and tibialis anterior, Irritation in S1 nerve root, without denervation. Based on overall investigations, and lack of evidence of alternative diagnosis, it was determined that the patient had Diabetic Amyotrophy. She refused IVIG, treated with prednisone 5mg PO oral for a month, Duloxetine and gabapentin, with significant improvement in pain and weakness. Patient was also connected with appropriate social services, physical and occupational therapy. Conclusion: Diagnostic delay of diabetic amyotrophy can lead to mental, physical, and financial debilitation. Due to low prevalence and broad differential of proximal muscle wasting, it is a challenging to diagnose and remains the diagnosis of exclusion. EMG studies with polyradiculopathy in proximal leg musculature is suggestive. Physicians should have a high clinical suspicion for diabetic amyotrophy to prevent long clinical course leading to harm to the patient. The emphasis is on creating awareness of the disease, and improving communication among clinicians and with patients, which are relatively minor investments to prevent delayed diagnosis of underrecognized complication. Presentation: Friday, June 16, 2023

ODP302 Cushing's Disease: A Challenging Diagnosis in Patients with Underlying Co-Morbidities

Abstract Introduction Cushing's disease (CD) is a rare endocrine disorder with significant morbidity and mortality. This case is a complicated ACTH (adrenocorticotropic hormone)-dependent hypercortisolism with a negative pituitary MRI inthe setting of underlying liver cirrhosis and chronic kidney disease. Hypercortisolism work up was challenging due to liver and kidney disease. Case Presentation A 42-year-old woman with a history of liver cirrhosis(MELDscore: 19) and stage 3b chronic kidney disease (CKD) presented with nausea, vomiting and abdominal pain. She reported proximal muscle weakness. On examination, she had central adiposity with large purple abdominal striae and proximal muscle wasting. Medical history was pertinent for uncontrolled hypertension and type 2 diabetes mellitus. Due to concern for Cushing's syndrome, an overnight 1 mg dexamethasone suppression test (DST) was performed. She had an inappropriately elevated morning cortisol of 10.1 mcg/dL (n < 1.8 mcg/dL), but suboptimal dexamethasone level of 104 ng/dL (140-295 ng/dL), suggesting incomplete absorption secondary to emesis. A repeat DST was not performed given concerns for reduced dexamethasone clearance with her underlying renal and liver disease. Her 24-hour urine free cortisol (UFC) was elevated at 55 ug/24 hr (6-42 ug/24 hr). A repeat 24-hour UFC was again elevated at 265 ug/24 hr (6-42 ug/24 hr). Three late night salivary cortisol levels were also elevated at 0.231 ug/dL, 0.429 ug/dL and 0.19 ug/dL (n <0. 01-0. 09 ug/dL). Diagnosis of Cushing's syndrome was confirmed. ACTH level obtained was detectable at 70.1 pg/mL (7.2-63.3 pg/mL), suggestive of ACTH-dependent Cushing's syndrome. Pituitary MRI without contrast was obtained due to CKD. MRI reported no pituitary abnormalities. High dose DST was not performed due to concerns for aforementioned reduced dexamethasone clearance and due to lack of availability of CRH (corticotropin-releasing hormone), CRH stimulation testing was not done. She underwent inferior petrosal sinus sampling (IPSS) which showed central to peripheral ACTH ratio of 2.11 at baseline and ratios of 3.53, 3.45 and 3.32 at 5 minutes, 10 minutes and 15 minutes respectively after vasopressin stimulation, solidifying the diagnosis of Cushing's disease. Patient is now scheduled for an exploration of the sella via endoscopic endonasal approach. Conclusion This case highlights the limitations of biochemical tests and imaging modalities in the workup of hypercortisolism, notably in patients with underlying liver and kidney disease. The ordering physician should be mindful of the caveats associated with each biochemical testing. ACTH-dependent Cushing's syndrome can be difficult to diagnose properly in the setting of a negative pituitary MRI. IPSS, although an expensive and invasive test, has the best diagnostic accuracy. This case further demonstrates the importance of performing an IPSS to diagnose CD and distinguish from an ectopic source when imaging is non-diagnostic. Presentation: No date and time listed

A recurrent rare intronic variant in CAPN3 alters mRNA splicing and causes autosomal recessive limb-girdle muscular dystrophy-1 in three Pakistani pedigrees.

Autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1) is an autosomal recessive disorder characterized by progressive weakness of the proximal limb and girdle muscles. Biallelic mutations in CAPN3 are reported frequently to cause LGMDR1. Here, we describe 11 individuals from three unrelated consanguineous families that present with typical features of LGMDR1 that include proximal muscle wasting, weakness of the upper and lower limbs, and elevated serum creatine kinase. Whole-exome sequencing identified a rare homozygous CAPN3 variant near the exon 2 splice donor site that segregates with disease in all three families. mRNA splicing studies showed partial retention of intronic sequence and subsequent introduction of a premature stop codon (NM_000070.3: c.379 + 3A>G; p.Asp128Glyfs*15). Furthermore, we observe reduced CAPN3 expression in primary dermal fibroblasts derived from an affected individual, suggesting instability and/or nonsense-mediated decay of mutation-bearing mRNA. Genome-wide homozygosity mapping and single-nucleotide polymorphism analysis identified a shared haplotype and supports a possible founder effect for the CAPN3 variant. Together, our data extend the mutational spectrum of LGMDR1 and have implications for improved diagnostics for individuals of Pakistani origin.

Late-Onset Melas with Midd: An Uncommon Age of Presentation

Objective: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes caused by a mutation in mitochondrial DNA, usually a point mutation at position 3243 in the leucine tRNA gene. This same mutation can cause a rare but severe syndrome called mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Methods: We describe a case of MIDD with acute mitochondrial decompensation that progressed to MELAS. Results: A 63-year-old male with MIDD and a history of hypoglycemic seizures presented for evaluation of altered mental status with fever, tachycardia, hypotension, and somnolence. His history was also significant for deafness and cochlear implants. The physical exam results were consistent with mild, proximal muscle wasting. The initial workup was concerning for sepsis and a urinary tract infection. Laboratory evaluation revealed lactic acidosis with normal white cell count, liver enzymes, and ammonia level. After fluid resuscitation and 4 days of broad-spectrum...

Revisit of a rare complication of type 1 diabetes mellitus: Mauriac syndrome

AbstractMauriac syndrome is an uncommon complication of poorly‐controlled type 1 diabetes mellitus (T1DM) reported in children 13–17 years of age. It manifests as delayed growth, hepatomegaly, elevated liver enzymes and serum lipids, and glycogen accumulation in hepatocytes. Common presenting features include short stature, growth retardation, moon facies, protuberant abdomen and proximal muscle wasting. Since the advent of long‐ and intermediate‐acting insulin, this syndrome is now rarely encountered.We report the case of a 16‐year‐old male who had a 13‐year history of T1DM and was diagnosed with Mauriac syndrome. He was treated with biphasic isophane insulin and recovered – good glycaemic control was maintained, his height increased from 128cm to 141.5cm, hepatomegaly disappeared with normal liver enzymes, and the onset of pubertal spurt at eight months' follow up was shown.In conclusion, ensuring compliance with insulin therapy, and providing supportive treatment, nutritional support and good follow‐up care can help to mitigate most of the complications relating to Mauriac syndrome. Copyright © 2017 John Wiley & Sons.

Subacute myopathy as the initial presentation of anca positive vasculitis associated with crohn’s disease

Objectives Myopathy as the presenting symptom from an ANCA positive vasculitis is uncommon. Vasculitis secondary to Crohn’s disease is an equally uncommon phenomenon. We report the first case of Crohn’s associated ANCA positive vasculitis causing a subacute proximal myopathy as the initial clinical manifestation. We also highlight the clinical improvement following institution of rituximab as rescue therapy. Case A 27 years old female with recently diagnosed active Crohn’s disease presented with a 9 months history of progressive proximal upper and lower limb weakness. She had been treated with a course of steroids 6 months prior. She denied any constitutional symptoms. Examination revealed proximal muscle wasting and weakness in both upper and lower limbs. Positive investigations included a positive ANCA with high PR3 titre and a muscle biopsy demonstrating probable vasculitis. She was diagnosed with myopathy secondary to Crohn’s associated ANCA-positive vasculitis. She was treated with adalumimab and then infliximab which was upgraded to rituximab as rescue therapy when there was no response. The rituximab led to significant improvement to her weakness clinically. Conclusions Vasculitis should be considered as a differential diagnosis for subacute myopathy in patients with an inflammatory or autoimmune phenotype. Muscle biopsy and ANCA immunofluorescence and titres are useful investigations. Whilst there is a lack of established evidence about the ideal agent for treating Crohn’s associated vasculitis, case reports suggest using TNF-alpha inhibitors or rituximab.

FRZB and melusin, overexpressed in LGMD2A, regulate integrin β1D isoform replacement altering myoblast fusion and the integrin-signalling pathway.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene. However, the underlying pathophysiological mechanisms of muscle degeneration are still not well understood. The objective of this study was to assess the relevance of genes with differential expression in the muscle of LGMD2A patients. For this purpose, we analysed their in vitro expression in primary cultures of human myoblasts and myotubes. Abnormal fusion was observed in the myotubes of these patients, which may be explained by the lack of physiological replacement of integrin β1D. Owing to this observation, we focused on deregulated genes coding proteins that directly interact with integrin, ITGB1BP2 and CD9, as well as FRZB gene, because of its in vitro upregulation in myotubes. Silencing studies established that these genes are closely regulated, CD9 and FRZB being positive regulators of the expression of ITGB1BP2, and in turn, this gene being a negative regulator of the expression of FRZB. Interestingly, we observed that FRZB regulates integrin β1D expression, its silencing increasing integrin β1D expression to levels similar to those in controls. Finally, the administration of LiCl, an enhancer of the Wnt-signalling pathway showed similar experimentally beneficial effects, suggesting FRZB silencing or LiCl administration as potential therapeutic targets, though further studies are required.

Multiple Endocrine Neoplasia Type II B with Simultaneous Papillary Microcarcinoma of Thyroid Gland – A Case Report

Multiple endocrine neoplasia (MEN) type II B is a rare disorder and represent 5% of multiple endocrine neoplasia type II. It is characterized by medullary thyroid carcinoma, pheochromocytoma and distinctive external morphological features like marfanoid habitus, mucosal neuromas, thickened eyelids, hypertrophied lips, slender body and proximal muscle wasting. Early diagnosis and surgical interventions for medullary thyroid carcinoma and pheochromocytoma results in improvement in long term survival. We report a case of multiple endocrine neoplasia type II B in a 20 years old male presented with distinct facial appearance, marfanoid habitus, everted eyelids, thick hypertrophied lips, mucosal neuromas and on and off giddiness, sweating and flushing of face. Clinical evaluation revealed sustained hypertension with episodes of superadded paroxysm and thickened corneal nerve on fundoscopic examination. Ultrasound of neck revealed bilateral thyroid nodules with enlarged regional neck glands and enlarged parathyroid glands. Contrast enhanced computerized scan of abdomen revealed a large left sided adrenal tumor. His serum calcitonin & serum and urinary catecholamines were raised with marginal elevation of serum calcium. Upper GI endoscopy revealed a vocal cord nodule. The patient underwent left sided radical adrenalectomy and total thyroidectomy three weeks later, with modified bilateral neck dissection together with parathyroidectomy and implantation of one of the parathyroid in the neck. Histopathology of the adrenal tumor was consistent with pheochromocytoma while thyroid gland was detected to harbor bilateral multicentric medullary carcinoma with simultaneous independent foci of papillary microcarcinoma. The patient is on follow up for last 9 yrs and is doing well.

Cushing's conundrum: an unusual case of primary pigmented nodular adrenal disease in a 60-year-old woman

A 60-year-old woman with resistant hypertension, poorly controlled type 2 diabetes, and chronic obstructive pulmonary disease requiring inhaled corticosteroids was referred for investigation of Cushing’s syndrome. She had a BMI of 31 kg/m2, abdominal obesity, and proximal muscle wasting. Investigations showed a normal aldosterone-to-renin ratio, plasma metanephrines, and renal artery Doppler ultrasound fi ndings, but increased 24 h urine free cortisol concentration (454 nmol/L [normal range <350 nmol/L]). Adrenocorticotropic hormone remained undetectable on several occasions for 12 months, during the diagnostic workup (<5 pg/mL). Because of diffi culty in ceasing use of inhaled corticosteroids, an overnight 1 mg dexa methasone suppression test was done while the patient was taking fl uticasone, showing an 8 am cortisol concentration of 278 nmol/L (compared with a normal range of <120 nmol/L). Persistent hypercortisolism was then confi rmed with intravenous dexamethasone suppression testing done after inhaled fl uticasone was withheld for several days. An adrenal CT scan showed an enlarged left adrenal gland, with an 8 mm nodule at the inferior pole (fi gure A), insuffi cient to account for the patient’s hypercortisolism. Functional imaging with iodo cholesterol under dexamethasone suppression showed bilateral uptake of labelled cholesterol (fi gure B). Adrenal vein sampling under dexamethasone supp ression was consistent with bilateral autonomous cortisol secretion (appendix). The patient underwent a bilateral adrenalectomy. The macroscopic and histological appearance was consistent with primary pigmented nodular adrenal hyperplasia (also known as primary pigmented nodular adrenal disease [PPNAD]; fi gure C, D). PPNAD is associated with Carney’s complex in 90% of white patients. Carney’s complex is an autosomal dominant multiple neoplasia syndrome, typically presenting with the classic triad of myxomas, spotty skin pigmentation, and endocrine overactivity. 60% of Carney’s complex in the white population is associated with germline-inactivating mutations in regulatory subunit 1α of protein kinase A (PRKAR1A). To our knowledge, this patient is the oldest reported person to be diagnosed with PPNAD—most patients are diagnosed before age 40 years. She has no other manifestations of Carney’s complex and is currently undergoing genetic testing for mutations in the PRKAR1A gene. This case shows that PPNAD can be latent for many years and should be considered in diff erential diagnosis of adrenocorticotropic hormoneindependent Cushing’s syndrome in elderly individuals.

Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

X-linked spinobulbar muscular atrophy (Kennedy’s disease) affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

P.15.12 Tubular aggregate myopathy caused by a heterozygous missense mutation in STIM1

This woman, now 33 years old, was first investigated at age 14 and previously described as a case report of tubular aggregate myopathy (Tulinius MH, Lundberg A, Oldfors A. Early-onset myopathy with tubular aggregates. Pediatric Neurol 1996;15:68–71). There was no family history of neuromuscular disease. Early motor milestones were normal. She never learned to run and at four years the parents noted she had a wide-based gait. At 12 years she lost the ability to rise from the squatting position without using her hands. The muscle weakness was slowly progressive over the years and she now presents with moderate proximal muscle weakness and wasting of both upper and lower extremities. She has slight ptosis and slight dysarthria but no ophthalmoplegia. CK has been constantly elevated 7–40 times upper normal levels. Muscle biopsy at age 14 and 30 years showed type 1 fiber predominance and numerous fibers (40–90% of all fibers), both type 1 and type 2, with tubular aggregates mainly located in the centre of the fibers and widely dispersed between myofibrils. Occasional necrotic fibers were present. Mutation analysis of STIM1 (stromal interaction molecule 1, the main Ca2 + sensor of the endoplasmic reticulum) revealed that the patient was heterozygous for a dominant missense mutation c.326A > G, p. p.His109Arg. This mutation was previously reported in two siblings in the original recent report describing mutations in STIM1 associated with tubular aggregate myopathy (Bohm J, Chevessier F, Maues De Paula A, et al. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet 2013;92:271–8).

A Young Male with Typical Presentation of Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular condition characterized by proximal and distal muscle wasting, weakness, fasciculation. The etiology of the disease is unknown. The annual incidence rate is one to two cases per 100,000 persons. The disease is most commonly presents in middle age, mostly after the age of 50 and very uncommon before the age of 30 years and affects men more than women. Usually it present with limb muscle weakness, cramps, occasionally fasciculations and sometimes with dysarthria, dysphagia. Symptoms often begin focally in one part and spread gradually but relentlessly to become widespread. Over a period of months or years, patients with ALS develop severe, progressive muscular weakness and other symptoms caused by loss of function in both upper and lower motor neurons. Sphincter control, sensory function, intellectual abilities and skin integrity are preserved. Patients become completely disabled, often requiring ventilatory support and gastrostomy. Death usually occurs within five years of diagnosis and is attributed to respiratory failure or cachexia. Current management involves aggressive, individualized alleviation of symptoms and complications. We are reporting an 18 year old right handed male presented with typical features of ALS . The purpose for reporting was for its rarity before 40 years and that had a typical clinical features of young-adult ALS, and to compare them with features of the common adult-onset type.&#x0D; Bangladesh Journal of Neuroscience 2013; Vol. 29 (2) : 134-138

Mauriac Syndrome: A Rare Complication of Poorly Controlled Diabetes Mellitus

Mauriac syndrome is one of the complications of poorly controlled diabetes mellitus type 1. Common presenting features include short stature, growth retardation, moon facies, protuberant abdomen, and proximal muscle wasting. We hereby report a case of 15 year old female who presented with clinical featues of Mauriac syndrome . Int J Clin Pediatr. 2013;2(2):76-77 doi: http://dx.doi.org/10.4021/ijcp103w

217 Use of liver ultrasound in assessment of cystic fibrosis liver disease in children

This survey was designed to assess the amount of variation around the UK in the investigation and management of CF related liver disease (CFLRD). Questionnaires were devised by a group of adult and paediatric CF physicians and also hepatologists and were sent to all major CF centres in the UK. 16 adult and 24 paediatric centres replied. The number of new CFLD cases ranged from 0−5 per year per centre. No centre carried out routine diagnostic liver biopsy and most centres did not use a severity scoring system. Non-invasive imaging other than ultrasound was mentioned by only 5 centres. In established CFLD, all centres monitored platelets, prothrombin time and albumin. Ultrasound monitoring varied between 6 monthly, annually or ad hoc. There was wide variation in screening for varices. Only 16 centres ran a joint clinic with a hepatologist but 38 centres had access to a hepatologist with a special interest in CFLD. Nearly all centres used lifelong URSO treatment for patients with, doses of 10−30mg/kg/day but only 5 centres used taurine. All adult centres advocated primary prophylaxis for grade 2+ varices and the majority preferred banding to beta blockade. Most centres considered triggers for referral for liver transplant to be one or more of: ascites, bleeding varices and impaired synthetic function but there was less consensus on proximal muscle wasting. 15 out of 40 centres felt that they did not have an adequate forum to discuss liver transplant issues. In summary, our survey showed wide variation in the assessment and management of CFLD in the UK with some differences compared to recent European guidance [1].

219 Prevalence of cystic fibrosis related liver disease in Northern Ireland

This survey was designed to assess the amount of variation around the UK in the investigation and management of CF related liver disease (CFLRD). Questionnaires were devised by a group of adult and paediatric CF physicians and also hepatologists and were sent to all major CF centres in the UK. 16 adult and 24 paediatric centres replied. The number of new CFLD cases ranged from 0−5 per year per centre. No centre carried out routine diagnostic liver biopsy and most centres did not use a severity scoring system. Non-invasive imaging other than ultrasound was mentioned by only 5 centres. In established CFLD, all centres monitored platelets, prothrombin time and albumin. Ultrasound monitoring varied between 6 monthly, annually or ad hoc. There was wide variation in screening for varices. Only 16 centres ran a joint clinic with a hepatologist but 38 centres had access to a hepatologist with a special interest in CFLD. Nearly all centres used lifelong URSO treatment for patients with, doses of 10−30mg/kg/day but only 5 centres used taurine. All adult centres advocated primary prophylaxis for grade 2+ varices and the majority preferred banding to beta blockade. Most centres considered triggers for referral for liver transplant to be one or more of: ascites, bleeding varices and impaired synthetic function but there was less consensus on proximal muscle wasting. 15 out of 40 centres felt that they did not have an adequate forum to discuss liver transplant issues. In summary, our survey showed wide variation in the assessment and management of CFLD in the UK with some differences compared to recent European guidance [1].

The many faces of SMN: deciphering the function critical to spinal muscular atrophy pathogenesis

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death, affecting 1 in 6000–10,000 live births. SMA is an autosomal recessive disorder characterized by the degeneration of α-motor neurons, and lower limb and proximal muscle weakness and wasting. SMA is the result of the deletion of or mutations in the survival motor neuron (SMN)1 gene. Currently, our understanding of how loss of the widely expressed SMN leads to the selective pathogenesis observed in SMA is limited. Here, we discuss the known nuclear and cytoplasmic functions of the SMN protein and how they relate to the SMA pathology reported in motor neurons, striated muscle and at neuromuscular junctions. While a vast amount of work in various cell and animal models has increased our knowledge of the many functions of the SMN protein, we have yet to come to a full understanding of which role(s) are central to SMA pathogenesis.

Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.

UP-1.012: Multiple Endocrine Neoplasia Type II B with Simultaneous Papillary Micro Carcinoma of Thyroid: A Case Report

Multiple endocrine neoplasia syndromes consist of rare autusomal dominant mutation in genes regulating cell growth. It is characterized by medullary thyroid carcinoma, pheochromocytoma and distinctive external morphological features like marfanoid habitus, mucosal neuromas, thickened eyelids, hypertrophied lips, slender body and proximal muscle wasting. However, associated parathyroid adenoma and papillary microcarcinoma of thyroid is extremely rare.

American Association Of Clinical Endocrinologists And American Association Of Endocrine Surgeons Medical Guidelines For The Management Of Adrenal Incidentalomas

American Association Of Clinical Endocrinologists And American Association Of Endocrine Surgeons Medical Guidelines For The Management Of Adrenal Incidentalomas