There are several basic principles for treatment of inborn errors of metabolism. Syndromes with toxicity often present with encephalopathy; removal of toxic compounds isthe first goal of therapy. Strategies include hemodialysis,hemovenovenous filtration, and administration of alternate pathway agents (see Chapter 53). A second strategy is toenhance deficient enzyme activity through administration ofenzyme cofactors (e.g., pyridoxine in homocystinuria, tetrahydrobiopterin in PKU). If deficiency of a pathway product plays an important role, providing missing products ishelpful (e.g., tyrosine in the treatment of phenylketonuria).A major principle is to decrease flux through the deficientpathway by restricting precursors in the diet. Examplesinclude the restriction of protein in disorders of ammoniadetoxification and of amino acid precursors in the organicacid disorders.
Many glycogen storage diseases are characterized by hypoglycemia and hepatomegaly (Table 52-1). Glycogen, the storage form of glucose, is found most abundantly in the liver (where it modulates blood glucose levels) and in muscles (where it facilitates anaerobic work). Glycogen is synthesized from uridine diphosphoglucose through the concerted action of glycogen synthetase and brancher enzyme (Fig. 52-1). The accumulation of glycogen is stimulated by insulin. Glycogenolysis occurs through a cascade initiated by epinephrine or glucagon. It results in rapid phosphorolysis of glycogen to yield glucose 1-phosphate, accompanied by, to a lesser degree, hydrolysis of glucose residues from the branch points in glycogen molecules. In the liver and kidneys, glucose 1-phosphate is converted to glucose 6-phosphate through the actions of phosphoglucomutase; glucose-6-phosphatase hydrolyses glucose 6-phosphate to produce glucose. The latter enzyme is not present in muscles. Glycogen storage diseases fall into the following four categories: 1.
Diseases that predominantly affect the liver and have a direct influence on blood glucose (types I, VI, and VIII) 2.
Diseases that predominantly involve muscles and affect the ability to do anaerobic work (types V and VII) 3.
Diseases that can affect the liver and muscles and directly influence blood glucose and muscle metabolism (type III) 4.
Diseases that affect various tissues but have no direct effect on blood glucose or on the ability to do anaerobic work (types II and IV)
The diagnosis of type I or type III glycogen storage disease is suggested by an elevated uric acid, lactate, and triglycerides in blood. For all forms, a diagnosis can normallybe confirmed by DNA mutation testing in white blood cells.When this is feasible, invasive procedures, such as muscleand liver biopsy, can be avoided. When mutation testing isnot available or is inconclusive, enzyme measurements intissue from the affected organ confirm the diagnosis. If thediagnosis cannot be established, metabolic challenge andexercise testing may be needed. Treatment of hepatic glycogen storage disease is aimed at maintaining satisfactory
Type 1a: Glucose-6-Liver, kidney, GI Hypoglycemia, lactic acidosis, Hypoglycemia, Early death from von Gierke phosphatase tract, platelets ketosis, hepatomegaly, lactic acidemia, hypoglycemia, lactic acidosis; hypotonia, slow growth, liver may not be do well with early diagnosis diarrhea, bleeding disorder, enlarged and strict adherence to gout, hypertriglyceridemia,
Type V: Muscle Muscle Muscle fatigue beginning in None Good, with sedentary lifestyle McArdle phosphorylase