NUTRITION

• Liver glycogenoses include Type Ia/Von Gierke, which causes growth retardation, hepatomegaly, hypoglycemia, elevated blood lactate, cholesterol, triglyceride, and uric acid levels, and is common and severe.
• Type Ib/Cori or Forbes causes the same symptoms as Type Ia, with additional findings of neutropenia, periodontal disease, and inflammatory bowel disease, and is 10% of Type Ia.
• Type IIIa/Cori or Forbes, also known as liver and muscle debrancher deficiency (amylo-1,6-glucosidase), causes hepatomegaly, growth retardation, muscle weakness, hypoglycemia, hyperlipidemia, and elevated transaminase levels, and is common and of intermediate severity of hypoglycemia.
• Type IIIb, also known as liver debrancher deficiency, causes the same symptoms as Type IIIa, but does not affect muscle enzyme activity, and is common.
• Type IV/Andersen, also known as branching enzyme, causes failure to thrive, hypotonia, hepatomegaly, splenomegaly, progressive cirrhosis, and elevated transaminase levels, and is rare.
• Type VI/Hers causes hepatomegaly, typically mild hypoglycemia, hyperlipidemia, and ketosis, and is often underdiagnosed, with severe presentation also known.
• Type IX/phosphorylase kinase (PhK) deficiency causes hypoglycemia, hyperketosis, hepatomegaly, chronic liver disease, hyperlipidemia, and elevated liver enzymes, and is common and X-linked.
• Type IXa (PHKA1 variant) causes exercise intolerance, cramps, myalgia, myoglobinuria, and no hepatomegaly, and is X-linked or autosomal recessive.
• Type II/Pompe infantile, also known as acid α-glucosidase (acid maltase) deficiency, causes cardiomegaly, hypotonia, hepatomegaly, and onset from birth to 6 months, and is common, with cardiorespiratory failure leading to death by age 1-2 years.
• Type II/Late-onset Pompe (juvenile and adult), also known as acid α-glucosidase (acid maltase) deficiency, causes myopathy, variable cardiomyopathy, respiratory insufficiency, and onset from childhood to adulthood, with residual enzyme activity.
• Type IIIa, also known as liver and muscle phosphorylase deficiency, causes hepatomegaly, growth retardation, and is common, with muscle weakness potentially progressing to need for ambulation assistance such as wheelchair.
• Type IIIb, also known as liver phosphorylase deficiency, causes hepatomegaly, growth retardation, and is common.
• Type IV, also known as branching enzyme, causes failure to thrive, hypotonia, hepatomegaly, splenomegaly, progressive cirrhosis, and elevated transaminase levels, and is rare.
• Type V/McArdle, also known as myophosphorylase deficiency, causes exercise intolerance, muscle cramps, myoglobinuria, and “second wind” phenomenon, and is common, with male predominance.
• Some patients with infantile Pompe disease who had peripheral nerve biopsies demonstrated glycogen accumulation in the neurons and Schwann cells.
• Diagnosis of Pompe disease can be made by enzyme assay in dried blood spots, leukocytes, blood mononuclear cells, muscle, or cultured skin fibroblasts demonstrating deficient acid α-glucosidase activity.
• Gene sequencing showing 2 pathogenic variants in the GAA gene is confirmatory.
• The enzyme assay should be done in a laboratory with experience using maltose, glycogen, or 4-methylumbelliferyl-α-D-glucopyranoside (4MUG) as a substrate.
• The infantile form of Pompe disease has a more severe enzyme deficiency than the late-onset forms.
• Detection of percent residual enzyme activity is captured in skin fibroblasts and muscle.
• Blood-based assays, especially dried blood spots, have the advantage of a rapid turnaround time and are being increasingly used as the first-line tissue to make a diagnosis.
• A muscle biopsy is often done with suspected muscle disease and a broad differential; it yields faster results and provides additional information about glycogen content and site of glycogen storage within and outside the lysosomes of muscle cells.
• A normal muscle biopsy does not exclude a diagnosis of Pompe disease.
• Late-onset patients show variability in glycogen accumulation in different muscles and within muscle fibers; muscle histology and glycogen content can vary depending on the site of muscle biopsy.
• There is a high risk from anesthesia in infantile patients.
• An electrocard>card>can be helpful in making the diagnosis in suspected cases of the infantile form and should be done for patients suspected of having Pompe disease before any procedure requiring anesthesia, including muscle biopsy, is performed.
• Urinary glucose tetrasaccharides can be elevated in the urine of affected patients, and levels are extremely high in infantile patients.
• GYG1 gene blocking glycogenin-1 biosynthesis results in a reduced or complete absence of glycogenin-1, a precursor necessary for glycogen formation.
• Defects in Metabolism of Carbohydrates GSD type V is caused by deficiency of myophosphorylase activity, which limits muscle ATP generation by glycogenolysis, resulting in muscle glycogen accumulation, and is the prototype of muscle energy disorders.
• Symptoms of GSD type V usually first develop in late childhood or in the 2nd decade of life.
• Clinical manifestations of GSD type V are generally characterized by exercise intolerance with muscle cramps and pain, and are precipitated by brief, high-intensity exercise, such as sprinting or carrying heavy loads, and less intense but sustained activity, such as climbing stairs or walking uphill.
• Metabolic Disorders: Polycystic ovaries can present findings consistent with polycystic ovary syndrome even though other features of polycystic ovary syndrome such as acne and hirsutism are not seen.
• Fertility appears to be normal in women with GSD I, as evidenced by several reports of successful pregnancy.
• Increased bleeding during menstrual cycles, including life-threatening menorrhagia, has been reported and could be related to the impaired platelet aggregation.
• Symptoms of gout usually start around puberty from long-term hyperuricemia.
• There is an increased risk of pancreatitis in patients with GSD I, secondary to the lipid abnormalities.
• The dyslipidemia, together with elevated erythrocyte aggregation, could predispose these patients to atherosclerosis, but premature atherosclerosis has not yet been clearly documented except for rare cases.
• Impaired platelet aggregation and increased antioxidative defense to prevent lipid peroxidation may function as a protective mechanism to help reduce the risk of atherosclerosis.
• Frequent fractures and radiographic evidence of osteopenia are common in patients with GSD I, and bone mineral content is reduced, even in prepubertal patients.
• By the 2nd or 3rd decade of life, some patients with type I GSD develop hepatic adenomas that can hemorrhage and turn malignant in some cases.