Glycogen storage disease type I history and symptoms: Difference between revisions
Irfan Dotani (talk | contribs) No edit summary |
|||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Glycogen storage disease type I}} | {{Glycogen storage disease type I}} | ||
{{CMG}} | {{CMG}}; {{AE}} | ||
{{PleaseHelp}} | |||
==Overview== | ==Overview== | ||
Clinical manifestations result, directly or indirectly, from | Clinical manifestations result, directly or indirectly, from | ||
| Line 9: | Line 12: | ||
#damage to tissue from hyperuricemia; | #damage to tissue from hyperuricemia; | ||
#in GSD Ib, bleeding and infection risk from blood cell effects. | #in GSD Ib, bleeding and infection risk from blood cell effects. | ||
==History and Symptoms== | ==History and Symptoms== | ||
Several different problems may lead to the diagnosis, usually by two years of age: | Several different problems may lead to the diagnosis, usually by two years of age: | ||
| Line 55: | Line 59: | ||
===Neurodevelopmental effects=== | ===Neurodevelopmental effects=== | ||
[[Developmental delay]] is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Because normal brain and muscle cells contain no glucose-6-phosphatase, GSD I causes no other neuromuscular effects. | [[Developmental delay]] is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Because normal brain and muscle cells contain no glucose-6-phosphatase, GSD I causes no other neuromuscular effects. | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
[[Category:Endocrinology]] | [[Category:Endocrinology]] | ||
[[Category:Hepatology]] | [[Category:Hepatology]] | ||
[[Category:Gastroenterology]] | [[Category:Gastroenterology]] | ||
{{WS}} | |||
{{WH}} | |||
Revision as of 15:51, 19 July 2016
|
Glycogen storage disease type I Microchapters |
|
Differentiating Glycogen storage disease type I from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Glycogen storage disease type I history and symptoms On the Web |
|
American Roentgen Ray Society Images of Glycogen storage disease type I history and symptoms |
|
Glycogen storage disease type I history and symptoms in the news |
|
Blogs on Glycogen storage disease type I history and symptoms |
|
Directions to Hospitals Treating Glycogen storage disease type I |
|
Risk calculators and risk factors for Glycogen storage disease type I history and symptoms |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Please help WikiDoc by adding content here. It's easy! Click here to learn about editing.
Overview
Clinical manifestations result, directly or indirectly, from
- inability to maintain an adequate blood glucose level during the post-absorptive hours of each day;
- organ changes due to glycogen accumulation;
- excessive lactic acid generation;
- damage to tissue from hyperuricemia;
- in GSD Ib, bleeding and infection risk from blood cell effects.
History and Symptoms
Several different problems may lead to the diagnosis, usually by two years of age:
- seizures or other manifestations of severe fasting hypoglycemia;
- hepatomegaly with abdominal protuberance;
- hyperventilation and apparent respiratory distress due to metabolic acidosis;
- episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia.
Hypoglycemia
Hypoglycemia is the central clinical problem, the one that is most damaging, and the one that most often prompts the initial diagnosis. Maternal glucose transferred across the placenta prevents hypoglycemia in a fetus with GSD I, but the liver is enlarged with glycogen at birth. The inability to generate and release glucose soon results in hypoglycemia, and occasionally in lactic acidosis fulminant enough to appear as a primary respiratory problem in the newborn period. Neurological manifestations are less severe than if the hypoglycemia were more acute. The brain's habituation to mild hypoglycemia is at least partly explained by use of alternative fuels, primarily lactate.
More commonly, infants with GSD I tolerate without obvious symptoms a chronic, mild hypoglycemia and compensated lactic acidosis between feedings. Blood glucose levels are typically 25 to 50 mg/dl (1.4-2.8 mM). These infants continue to need oral carbohydrates every few hours. Many never sleep through the night even in the second year of life. They may be pale, clammy, and irritable a few hours after a meal. Developmental delay is not an intrinsic or inevitable effect of glucose-6-phosphatase deficiency but is common if the diagnosis is not made in early infancy.
Although mild hypoglycemia for much of the day may go unsuspected, the metabolic adaptations described above make severe hypoglycemic episodes, with unconsciousness or seizure, uncommon before treatment. Episodes which occur are likely to happen in the morning before breakfast. GSD I is therefore a potential cause of ketotic hypoglycemia in young children.
Once the diagnosis has been made, the principal goal of treatment is to maintain an adequate glucose level and prevent hypoglycemia.
Hepatomegaly and liver problems
Impairment of glycogenolysis also causes the characteristic enlargement of the liver due to accumulation of glycogen. Glycogen also accumulates in kidneys and small intestine. Hepatomegaly, usually without splenomegaly, begins to develop in fetal life and is usually noticeable in the first few months of life. By the time the child is standing and walking, the hepatomegaly may be severe enough to cause the abdomen to protrude. The liver edge is often at or below the level of the umbilicus. Other liver functions are usually spared, and liver enzymes and bilirubin are usually normal.
However, there is a risk of developing tumors of the liver by adolescence or adult ages, and periodic ultrasound examinations of the liver are recommended from late childhood onward. Occasional cases of various types of liver disease and failure have been reported in children and adults with GSD I.
Lactic acidosis
Impaired gluconeogenesis results in elevations of lactic acid (4-10 mM) even when the child is well. In an episode of metabolic decompensation, lactic acid levels abruptly rise and can exceed 15 mM, producing severe metabolic acidosis. Uric acid, ketoacids, and free fatty acids further increase the anion gap. Manifestations of severe metabolic acidosis include vomiting and hyperpnea, which can exacerbate hypoglycemia by reducing oral intake. Repeated episodes of vomiting with hypoglycemia and dehydration may occur in infancy and childhood, precipitated by (or mimicking) infections such as gastroenteritis or pneumonia.
Growth failure
Without treatment, growth failure is common, due to chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, calorie insufficiency, and/or malabsorption.
Hyperlipidemia and blood vessel effects
A secondary effect of low insulin levels is hypertriglyceridemia. Triglycerides in the 400–800 mg/dl range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the serum. Cholesterol is only mildly elevated.
Hyperuricemia and joint problems
A further effect of chronic lactic acidosis in GSD I is hyperuricemia, as lactic acid and uric acid compete for the same renal tubular transport mechanism. Increased purine catabolism is an additional contributing factor. Uric acid levels of 6-12 mg/dl are typical of GSD I.
Kidney effects
Kidneys are usually 10 to 20% enlarged with stored glycogen. This does not usually cause clinical problems in childhood, with the occasional exception of a Fanconi syndrome with multiple derangements of renal tubular reabsorption, including proximal renal tubular acidosis with bicarbonate and phosphate wasting. However, prolonged hyperuricemia can cause uric acid nephropathy. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to renal failure.
Bowel effects
Intestinal involvement can cause mild malabsorption with sloppy stools but usually requires no treatment.
Infection risk
Blood clotting problems
Impaired platelet aggregation is an uncommon effect of chronic hypoglycemia. It may cause clinically significant bleeding, especially epistaxis.
Neurodevelopmental effects
Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Because normal brain and muscle cells contain no glucose-6-phosphatase, GSD I causes no other neuromuscular effects.