1,721,360 research outputs found
Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.
Full text linkMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking
Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement.
No full textMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive metabolic disorder caused by a deficiency of thymidine phosphorylase (TP, EC2.4.2.4) due to mutations in the nuclear gene TYMP. TP deficiency leads to plasma and tissue accumulations of thymidine and deoxyuridine which generate imbalances within the mitochondrial nucleotide pools, ultimately leading to mitochondrial dysfunction.1 MNGIE is characterized clinically by leukoencephalopathy, external ophthalmoplegia, peripheral polyneuropathy, cachexia, and enteric neuromyopathy manifesting as gastrointestinal dysmotility. The condition is relentlessly progressive, with patients usually dying from a combination of nutritional and neuromuscular failure at an average age of 37 years.2 Allogeneic hematopoietic stem cell transplantation (AHSCT) offers a permanent cure. Clinical and biochemical improvements following AHSCT have been reported but it carries a high mortality risk and is limited by matched donor availability.3 A consensus proposal for standardizing AHSCT recommends treatment of patients without irreversible end-stage disease and with an optimally matched donor; a majority of patients are ineligible and thus there is a critical requirement for an alternative treatment
Mitochondrial diseases: A nosological update
No full textMitochondrial diseases are disorders caused by impairment of the mitochondrial respiratory chain, characterized by clinical-genetic heterogeneity and frequent multisystemic involvement. It is difficult to establish a precise genotype/phenotype correlation and obtain a definitive nosology. Today's genetic classification distinguishes disorders caused by defects in the mitochondrial genome (sporadic or maternally-inherited) from disorders caused by defects in the nuclear genome (autosomally-inherited). We report an updated classification, briefly review the main clinical syndromes and describe the most recent genetic knowledge. © 2007 The Authors
Multidisciplinary neurological and pneumological management of patients with glycogenosis type II
No full textGlycogenosis type II is a progressive, multisystemic and often disabling disorder that affects patients' quality of life and survival. Traditionally, three clinical forms of the disease have been classified based on age of symptoms onset: classic infantile-onset, non-classic infantile-onset and late-onset. A correct management of glycogenosis type II patients requires early intervention by a multidisciplinary team with different specialists involved. In this contest, pulmonologists play a crucial role especially in late-onset glycogenosis type II, opening a complete new scenario for them with the management of new, "unknown" patients. Thus, finding a unique approach for the diagnosis, treatment and management of glycogenosis type II patients, involving both neurologists and pulmonologists, becomes of paramount importance. Expected results of this approach should be: highly specific, non invasive and inexpensive diagnostic tools, modern rehabilitation programs, proper management of emergencies and proper chronic care. In addition, new outcomes based on patients and family satisfaction and on the reduction of hospitalization complications should be sought. Here, we present the main concepts on the diagnosis, treatment and management of glycogenosis type II and we suggest a possible collaborative approach for neurologists and pulmonologists
Magnetic Resonance Imaging of the Peripheral Nerve
No full textThe diagnostic workup of peripheral neuropathies has traditionally relied on the patient’s clinical history, physical examination, and electrophysiological studies [1]
Critical illness myopathy
No full textPurpose of review. To describe the incidence, major risk factors, and the clinical, electrophysiological, and histological features of critical illness myopathy (CIM). Major pathogenetic mechanisms and long-term consequences of CIM are also reviewed.
Recent findings. CIM is frequently associated with critical illness polyneuropathy (CIP), and may have a relevant impact on patients’ outcome. CIM has an earlier onset than CIP, and recovery is faster. Loss of myosin filaments on muscle biopsy is important to diagnose CIM, and has a good prognosis. Critical illness, use of steroids, and immobility concur in causing CIM.
Summary. A rationale diagnostic approach to CIM using clinical, electrophysiological, and muscle biopsy investigations is important to plan adequate therapy and to predict recovery
Critical illness myopathy.
No full textPURPOSE OF REVIEW: To describe the incidence, major risk factors, and the clinical, electrophysiological, and histological features of critical illness myopathy (CIM). Major pathogenetic mechanisms and long-term consequences of CIM are also reviewed.
RECENT FINDINGS: CIM is frequently associated with critical illness polyneuropathy (CIP), and may have a relevant impact on patients' outcome. CIM has an earlier onset than CIP, and recovery is faster. Loss of myosin filaments on muscle biopsy is important to diagnose CIM, and has a good prognosis. Critical illness, use of steroids, and immobility concur in causing CIM.
SUMMARY: A rationale diagnostic approach to CIM using clinical, electrophysiological, and muscle biopsy investigations is important to plan adequate therapy and to predict recovery
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