Glycogen Storage Diseases

Type

1. von-Gierke: G6Pase deficiency: severe fasting hypoglycemia, gout at puberty
2. Pompe: alpha-glucosidase (acid maltase, lysosomal enzyme) deficiency: hypotonia, then heart failure
3. Cori: glycogen debranching deficiency: presents like type 1
4. Anderson: glycogen-branching enzyme deficiency: progressive liver cirrhosis
5. McArdle: muscle phosphorylase deficiency: exercise intolerance

GSD Type 0

• Unlike other forms of glycogen-storage disease, GSD-0 does not involve the storage of excessive or abnormal glycogen and is characterized by decreased glycogen stores in the liver.
  commonly appears in infancy and early childhood with fasting hypoglycemia accompanied by ketosis and reference range blood levels of lactate and alanine.
• Although feeding relieves symptoms, it results in postprandial hyperglycemia and hyperlacticacidemia.

GSD Type 1: Von Gierke

• deficiency of glucose-6-phosphatase
• autosomal recessive
• accumulation of glycogen in liver (hepatomegaly, fatty liver) and kidneys (enlarged, renal dz)
• PE: doll-face facies, tendon xanthomas, hepatomegaly
• Present when they begin to sleep through the night
• labs:
  • severe fasting hypoglycemia; If give epi/glucagon, no rise in blood glucose, but do see increased lactic acid
  • hyperuricemia: gout at puberty
  • hyperlipidemia
  • impaired platelet function: prolonged PT, hx of bruising easily
• treatment: avoidance of fasting and frequent administration of carbohydrates; in infants, NG feedings may be useful at night. Uncooked cornstarch (slow release of glucose) is a mainstay of treatment in infant and children.
• vs other GSD's
  • vs type III (Cori's dz), in which there is no renal involvement
  • vs type V (McArdles) in which skeletal muscle is involved

GSD Type 2: Pompe

• fatal during the first year of life
• autosomal recessive
• deficiency in lysosomal enzyme: alpha-1,4-glucosidase (=acid maltase)
  • required for the degradation of a small percentage (1-3%) of cellular glycogen
  • deficiency causes accumulation of structurally normal glycogen in lysosomes and cytoplasm
  • the main pathway for glycogen degradation is not deficient in GSDII disease,so hypoglycemia does not occur
• accumulation of glycogen in heart, muscle, kidney, liver, lungs
• present with weakness and hypotonia in the first 6 months of life, which may manifest as respiratory and feeding difficulties.
• PE: macroglossia, hepatomegaly, significant generalized muscular flaccidity.
• death from cardiopulmonary failure in first year of life

GSD Type 3: Cori's Disease

• glycogen debranching enzyme deficiency
• the glycogen molecule has an abnormal structure: extensively hydrolyzed by phosphorylase (ie, the enzyme that cleaves the alpha1,4-glycosidic bonds that form the linear backbone of glycogen) but that contained all of the alpha1,6-glycosidic bonds that formed the branch points of the original glycogen molecule.
• Features: Hypoglycemia (Hypoglycemia is rare in neonates but often manifests at age 3-4 months, an age when many parents reduce feeding frequency), liver damage, Skeletal myopathy and cardiomyopathy, hyperlipidemia, hyperlipidemia; clinical manifestations of GSD III, even within the various subtypes, vary dramatically from patient to patient.
• Vs GSD I - Von Gierke: Clinical presentation of these diseases in children aged 3-8 years may be almost indistinguishable.

GSD Type 4: Anderson Disease

• Deficient glycogen-branching enzyme activity causes abnormal glycogen with long, unbranched outer chains and decreased solubility
• involving the liver, heart, muscle, skin, intestine, brain, spinal cord, and peripheral nerve.
• Classic presentation of hepatosplenomegaly and failure to thrive during the first year of life
• followed by progressive liver cirrhosis with portal hypertension and death, usually by the age of 5 years.
• GSD IV exhibits clinical heterogeneity with variable age of onset, specific organ involvement, and degree of accumulation of abnormal glycogen in different tissues.
• Progressive liver cirrhosis characterizes the classic form of GSD IV.
• Patients with nonprogressive liver disease and later onset represent a milder variant.
• In addition to these hepatic forms, several neuromuscular forms of GSD IV recently have been identified.
• A common variant involves isolated or predominant muscle involvement with the development of myopathy or cardiomyopathy during childhood. A
•  perinatal form is distinguished by severe neuromuscular involvement and death.
• Finally, a subset of patients with clinically diagnosed adult polyglucosan body disease (APBD) have deficient glycogen-branching enzyme activity and diffuse CNS and peripheral nervous system dysfunction.

GSD Type 5: McArdle's Disease

• deficiency of myophosphorylase (alpha-1,4-glucan orthophosphate glycosyl transferase), which normally initiates glycogen breakdown by removing 1,4-glucosyl groups from the glycogen molecule with release of glucose-1-phosphate.
• The symptoms experienced by patients with McArdle disease most likely are caused by the pattern of fuel utilization of exercising muscle.
• typical features of McArdle disease include exercise intolerance with myalgia, early fatigue, and stiffness of exercising muscles, which are relieved by rest. Following a short period of rest, most patients experience a second wind phenomenon and can resume exercise without difficulty. About one half of the patients suffer from acute muscle necrosis and myoglobinuria following vigorous exercise, and some may develop renal failure. Reports exist of a fatal infantile form of McArdle disease with hypotonia, generalized muscle weakness, and progressive respiratory insufficiency. In addition, a late-onset form exists with no symptoms until the sixth decade of
  life.

GSD 6

Glycogen-storage disease type VI (GSD VI) represents a heterogeneous group of hepatic glycogenoses with mild clinical manifestations and benign course. Patients typically exhibit prominent hepatomegaly, growth retardation, and variable but mild episodes of fasting hypoglycemia and hyperketosis during childhood. Hyperlacticacidemia and hyperuricemia characteristically are absent. In addition, patients may demonstrate elevated serum transaminases, hyperlipidemia, hypotonia, and muscle weakness. These clinical features and biochemical abnormalities generally resolve by puberty. Rare variants may have associated proximal renal tubule acidosis, myopathy, or fatal cardiomyopathy.

In general, GSD VI is caused by defects in the hepatic glycogen phosphorylase-activating system. The classic form of GSD VI results from a primary deficiency of liver phosphorylase. Other defects of the phosphorylase cascade system now included in this form of GSD are phosphorylase b kinase deficiency (formerly GSD IX, GSD VIII by McKusick) and adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase deficiency (formerly GSD X).

GSD 7: phosphofructokinase (PFK) deficiency

Reference:

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