Metabolic disorders include a wide array of diseases affecting a number of important pathways that frequently result in neurological consequences. The advances in biochemistry and molecular genetics have revealed much about these disorders. As with most technological advances, as the disorders are better defined, more closely related variants emerge. This further complicates the clinical and diagnostic picture for the pediatrician and subspecialist alike. The introductory section of Chapter 24 discusses these issues in greater detail. The same factors apply to the metabolic disorders, and there is considerable overlap between these two categories of disease.
An often overlooked component of the management of these disorders is a coordinated genetic counseling program. This is more than simply advising a family that a disease is hereditary. There should be coordinated genetic, reproductive, and medical counseling and management.1
Table 23-1 gives an overview of the glycogen storage diseases (GSDs).
Table 23–1. Glycogen Storage Disease Quick Reference Table ||Download (.pdf)
Table 23–1. Glycogen Storage Disease Quick Reference Table
|Type||Eponym||Defect||Involved Tissue||Special Features|
|I||Von Gierke||Glucose-6-phosphatase||Liver, kidney||Hypoglycemic seizures|
|II||Pompe||Acid maltase||Generalized||Floppy baby|
|V||McArdle||Muscle phosphorylase||Muscle||Cramps, weakness|
|VI||—||Liver phosphorylase||Liver, WBC||Hypoglycemia|
|VII||Tarui||Phosphofructokinase||Muscle, RBC||Cramps, weakness|
Acid Maltase Deficiency—Pompe Disease
Biochemistry and Clinical Characteristics
Acid maltase deficiency (AMD), or Pompe disease (Box 23-1), is an autosomal recessive (AR) glycogen storage disease with several different manifestations.2 Infantile AMD manifests itself within weeks of birth. The clinical manifestations include floppy baby syndrome, generalized and bulbar weakness, macroglossia, cardiomegaly, and hepatomegaly. The symptoms progress to death by age 2 years.
Box 23-1. Pompe Disease ||Download (.pdf)
Box 23-1. Pompe Disease
- Common Name: Pompe disease
- Inheritance: Autosomal recessive
- Metabolic Defect: Acid maltase deficiency
- Clinical Pattern: Infantile AMD: floppy baby syndrome, generalized and bulbar weakness, macroglossia, cardiomegaly, and hepatomegaly, progressing to death by age 2 years.
Adult AMD, on the other hand, usually starts in the twenties or thirties. The clinical presentation is different in this population, with the primary findings being respiratory weakness more prominent than limb-girdle weakness and intracranial aneurysms secondary to glycogen accumulation in vessels.
The evaluation of AMD reveals increased creatine kinase (CK) with a normal ischemic exercise test. The needle EMG reveals evidence of myopathy and electrical myotonia without clinical myotonia. There is a vacuolar myopathy with accumulation of PAS-positive material in lysosomes on microscopic evaluation (Figure 23-1).