|
|
| (73 intermediate revisions by 3 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {{Glycogen storage disease type I}}
| |
|
| |
|
| {{CMG}}; {{AE}} {{Anmol}} | | {{CMG}}; {{AE}} {{Anmol}} |
|
| |
|
| | | ==Tables== |
| =Pathophysiology=
| | {| class="wikitable" |
| ==Pathophysiology==
| | |+ |
| *GSD type 1 results due to defects in either hydrolysis or transport of glucose-6-phosphate
| | !Diagnosis |
| *GSD type 1a is due to the deficiency of enzyme glucose-6-phosphatase (G6Pase).
| | !Lab findings |
| *GDS type 1b is due to defect in glucose-6-phosphate translocase (T1 deficiency).
| | ! |
| *G6Pase is primarily expressed in expressed primarily in the gluconeogenic the liver and kidney. It is also expressed to a lesser extent in the intestine and pancreas.
| | ! |
| *Glucose-6-phosphatase catalyzes the conversion of glucose-6-phosphate to glucose during glycogenolysis and gluconeogenesis.
| | |- |
| *This defects hinders the conversion of glucose-6 phosphate to glucose in organs.
| | ! |
| *This leads to accumulation of glycogen in organs including liver, kidney, and intestine.
| | ! |
| *The inability of glucose-6-phosphate to leave cells leads to severe fasting hypoglycemia.
| | ! |
| *This also results in the development of various secondary metabolic and biochemical abnormalities including hyperlactacidemia, hyperuricemia, and hyperlipidemia.
| | ! |
| | | |- |
| ===Hepatomegaly and liver disorders===
| | | |
| *Impairment of glycogenolysis leads to the accumulation of fat and glycogen deposition resulting in characteristic hepatomegaly.
| | | |
| *Hepatomegaly is more pronounced when the child is young and decreases as the age progresses. The hepatomegaly leads to protrusion of the abdomen.
| | | |
| *Patients with GSD type 1 may develop hepatic lesions including:
| | | |
| **Hepatocellular adenoma (most common)
| | |- |
| **HCC
| | | |
| **Hepatoblastoma
| | | |
| **Focal fatty infiltration
| | | |
| **Focal fatty sparing
| | | |
| **Focal nodular hyperplasia
| | |- |
| **Peliosis hepatis
| | | |
| *The prevalence of hepatocellular adenoma increases as the age progress. 70 - 80 % Patients have at least one lesion of hepatocellular adenoma by the time they reach the age of 25 years.
| | | |
| | | | |
| ===Renal disorders===
| | | |
| *Patients with GSD type 1 have renal manifestations early in childhood.
| | |} |
| *Glycogen deposits in kidneys leading to nephromegaly, which is usually detected by imaging techniques.
| |
| *There is a progressive decrease in urinary citrate excretion as the age increases. Hypocitraturia along with hypercalciuria leads to nephrolithiasis and nephrocalcinosis.<ref name="pmid11241046">{{cite journal| author=Weinstein DA, Somers MJ, Wolfsdorf JI| title=Decreased urinary citrate excretion in type 1a glycogen storage disease. | journal=J Pediatr | year= 2001 | volume= 138 | issue= 3 | pages= 378-82 | pmid=11241046 | doi=10.1067/mpd.2001.111322 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11241046 }} </ref><ref name="pmid8747109">{{cite journal| author=Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV| title=Glomerular and tubular function in glycogen storage disease. | journal=Pediatr Nephrol | year= 1995 | volume= 9 | issue= 6 | pages= 705-10 | pmid=8747109 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8747109 }} </ref><ref name="pmid8441093">{{cite journal| author=Restaino I, Kaplan BS, Stanley C, Baker L| title=Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease. | journal=J Pediatr | year= 1993 | volume= 122 | issue= 3 | pages= 392-6 | pmid=8441093 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8441093 }} </ref>
| |
| *Glycogen storage and metabolic disturbances in patients with GSD type 1 leads to progressive glomerular injury and finally end-stage renal disease requiring renal transplantation.
| |
| | |
| ===Hematologic Disorders===
| |
| ====Anemia====
| |
| *Anemia in GSD type 1 is due to an array of factors including:<ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref><ref name="pmid22678084">{{cite journal| author=Wang DQ, Carreras CT, Fiske LM, Austin S, Boree D, Kishnani PS et al.| title=Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib. | journal=Genet Med | year= 2012 | volume= 14 | issue= 9 | pages= 795-9 | pmid=22678084 | doi=10.1038/gim.2012.41 | pmc=3808879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22678084 }} </ref>
| |
| **The restricted nature of the diet
| |
| **Chronic lactic acidosis
| |
| **Renal disorders
| |
| **Bleeding diathesis
| |
| **Chronic nature of the illness
| |
| **Suboptimal metabolic control
| |
| **Hepatic adenomas
| |
| **Inflammatory bowel disease (specifically in GSD type 1b)
| |
| *Abnormal expression of hepacidin in GSD type 1 leads to refractory iron deficiency anemia.<ref name="pmid12393428">{{cite journal| author=Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC| title=Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. | journal=Blood | year= 2002 | volume= 100 | issue= 10 | pages= 3776-81 | pmid=12393428 | doi=10.1182/blood-2002-04-1260 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12393428 }} </ref>
| |
| *In GSD type 1b associated with inflammatory bowel disease is believed to be due to Interleukin-6. Increased expression of Interleukin-6 due to inflammation leads to upregulation of hepcidin leading to anemia.
| |
| | |
| ====Bleeding diathesis====
| |
| *Bleeding diathesis in GSD type 1 secondary to metabolic abnormalities and include:<ref name="pmid4350560">{{cite journal| author=Czapek EE, Deykin D, Salzman EW| title=Platelet dysfunction in glycogen storage disease type I. | journal=Blood | year= 1973 | volume= 41 | issue= 2 | pages= 235-47 | pmid=4350560 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4350560 }} </ref><ref name="pmid4212074">{{cite journal| author=Corby DG, Putnam CW, Greene HL| title=Impaired platelet function in glucose-6-phosphatase deficiency. | journal=J Pediatr | year= 1974 | volume= 85 | issue= 1 | pages= 71-6 | pmid=4212074 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4212074 }} </ref><ref name="pmid942229">{{cite journal| author=Hutton RA, Macnab AJ, Rivers RP| title=Defect of platelet function associated with chronic hypoglycaemia. | journal=Arch Dis Child | year= 1976 | volume= 51 | issue= 1 | pages= 49-55 | pmid=942229 | doi= | pmc=1545862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=942229 }} </ref>
| |
| *Acquired platelet dysfunction with prolonged bleeding times
| |
| *Decreased platelet adhesiveness
| |
| *Abnormal aggregation of platelets
| |
| | |
| ====Neutropenia and neutrophil dysfunction====
| |
| *Neutropenia and neutrophil dysfunction is specific fo GSD type 1b.<ref name="pmid12373578">{{cite journal| author=Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K et al.| title=Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S83-7 | pmid=12373578 | doi=10.1007/s00431-002-1010-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373578 }} </ref>
| |
| *Neutropenia and neutrophil dysfunction in glycogen storage disease type Ib is thought to be due to loss of glucose-6-phosphate translocase activity leading to:<ref name="pmid19741523">{{cite journal| author=Chou JY, Jun HS, Mansfield BC| title=Neutropenia in type Ib glycogen storage disease. | journal=Curr Opin Hematol | year= 2010 | volume= 17 | issue= 1 | pages= 36-42 | pmid=19741523 | doi=10.1097/MOH.0b013e328331df85 | pmc=3099242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19741523 }} </ref>
| |
| **Enhanced endoplasmic reticulum stress
| |
| **Oxidative stress
| |
| **Apoptosis of neutrophils
| |
| *Patients with GSD type 1b associated with neutropenia are at increased risk of:
| |
| **Infections
| |
| **Gingivitis
| |
| **Mouth ulcers
| |
| **Upper respiratory infections
| |
| **Deep abscesses
| |
| **Enterocolitis
| |
| *Also, there is dysfunction of monocytes leads to:<ref name="pmid2164043">{{cite journal| author=Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley CA, Baker L et al.| title=Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b. | journal=J Clin Invest | year= 1990 | volume= 86 | issue= 1 | pages= 196-202 | pmid=2164043 | doi=10.1172/JCI114684 | pmc=296707 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2164043 }} </ref>
| |
| **Granuloma formation
| |
| **Chronic inflammatory responses
| |
| | |
| ==Genetics==
| |
| *80% Cases of GSD 1 are of GSD type 1a.<ref name="pmid10322403">{{cite journal| author=Mansfield BC| title=Molecular Genetics of Type 1 Glycogen Storage Diseases. | journal=Trends Endocrinol Metab | year= 1999 | volume= 10 | issue= 3 | pages= 104-113 | pmid=10322403 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10322403 }} </ref>
| |
| *G6Pase gene is located on chromosome locus 17q21.
| |
| *Glucose-6-phosphate translocase is located on chromosome locus 11q23.
| |
| *GSD type 1 follows an autosomal recessive pattern.
| |
|
| |
|
| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |