Glycogen Storage Disease Type III diagnosis and management guidelines

Department of Pediatrics, University of Groningen, Groningen, Groningen, Netherlands
Genetics in medicine: official journal of the American College of Medical Genetics (Impact Factor: 7.33). 07/2010; 12(7):446-63. DOI: 10.1097/GIM.0b013e3181e655b6
Source: PubMed


Disclaimer: ACMG standards and guidelines are designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticists should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.

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Available from: Areeg El-gharbawy, Dec 28, 2013
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    • "In summary, rhGAA therapy has dramatically improved the outcome of patients with classical infantile Pompe disease but still raises important ethical problems (Kishnani et al. 2010b). While ERT should start as soon as possible, it is not known in many cases whether the infant will respond well or not. "
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    ABSTRACT: Purpose: Enzyme replacement therapy (ERT) has been shown to improve outcome in classical infantile Pompe disease. The purpose of this study was to assess mortality, morbidity, and shortcomings of ERT in a larger cohort of patients treated outside clinical trials. To accomplish this, we retrospectively analyzed the data of all 23 subjects with classical infantile Pompe disease having started ERT in Germany between January 2003 and December 2010. Results: Ten patients (43%) deceased and four others (17%) became ventilator dependent. Seven infants (30.5%) made no motor progress at all, while seven (30.5%) achieved free sitting, and nine (39%) gained free walking. Besides all the seven patients (100%) attaining no improvement of motor functions, four out of the seven (57%) achieving to sit without support, and three out of the nine (33%) being able to walk independently, secondarily deteriorated, and died or became ventilator dependent. Sustained reduction of systolic function despite reversal of cardiac hypertrophy (n = 3), gastroesophageal reflux (n = 5), swallowing difficulties or failure to thrive (n = 11), recurrent pneumonias (n = 14), port system complications (n = 4), anesthesia-related incidents (n = 2), severe allergic reactions (n = 6), hearing loss (n = 3), and orthopedic deformities (n = 4) were problems frequently encountered. Conclusion: Although this study has important shortcomings due to its retrospective nature and because important variables potentially influencing outcome were not available for a substantial amount of patients, these data suggest that classical infantile Pompe disease still remains a life-threatening condition associated with high morbidity and often dismal prognosis. Currently, a relevant number of patients do not benefit definitely from ERT.
    Full-text · Article · Jan 2015
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    • "Patients with persistent abnormal liver function, lipid profiles and muscle weakness may have one of many genetic disorders, including fatty acid oxidative disorders (FAOD) and glycogen storage disorders [9] [10]. Patients with FAOD may present a broad spectrum of clinical symptoms, ranging from a complete absence of symptoms to extreme sleepiness, poor appetite, nausea, diarrhea http://dx.doi. "
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    ABSTRACT: We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients' cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.
    Full-text · Article · Oct 2014 · Biochemical and Biophysical Research Communications
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    • "The glycogen structure is abnormal with short peripheral chains and is called limit-dextrin. Usual recommendations include frequent meals, high-carbohydrate and high protein intake and raw cornstarch or continuous feeding during the night, which prevent fasting hypoglycemia but do not influence the course of cardiac and muscular manifestations [29]. Recently, Valayannopoulos et al. [30] proposed an experimental treatment to a two-month old infant with a severe familial form of GSDIII complicated by severe cardiomyopathy, whose sister had died of severe cardiomyopathy on standard nutritional protocol. "
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    ABSTRACT: Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested by either a metabolic crisis with weakness, sometime associated to respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset form, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, Neutral Lipid Storage - Myopathy (NLSD-M), beside RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
    Full-text · Article · Jul 2014 · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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