Management of Lysosomal Storage Disorders

Diagnostic Confirmation

Diagnosis of lysosomal storage disorders must be established through specific enzyme assays and mutational analysis, as clinical presentations can vary widely, according to the American College of Medical Genetics and Genomics 1
Urinary mucopolysaccharides and oligosaccharides may be useful for screening but can be normal or nonspecifically elevated in healthy neonates, as noted by the American College of Medical Genetics and Genomics 1
Presymptomatic individuals may be identified through newborn screening, family-based testing after proband identification, carrier screening, or prenatal testing, as recommended by the American College of Medical Genetics and Genomics 3

The American College of Medical Genetics and Genomics recommends enzyme replacement therapy as the most widely used treatment for LSDs, supplying the missing enzyme through repeated intravenous infusions 2
Enzyme replacement therapy is available for several LSDs including Fabry disease, Gaucher disease, Pompe disease, and certain mucopolysaccharidoses, according to the American College of Medical Genetics and Genomics 2
The decision to initiate enzyme replacement therapy should be made according to clinical judgment of the managing metabolic physician in conjunction with the patient's family, as advised by the Society for Inherited Metabolic Disorders 4

The American Society of Hematology notes that hematopoietic stem cell transplantation has been used successfully in the management of some LSDs, providing a reconstituted hematopoietic system from a healthy donor that produces the missing enzyme 2
Hematopoietic stem cell transplantation has the advantage of allowing cells to integrate into many tissues, including the central nervous system, as reported by the American Society of Hematology 2

The European Medicines Agency approves the use of substrate reduction therapy, such as miglustat, which works by stabilizing misfolded but functional enzymes as they are synthesized in the endoplasmic reticulum, as noted by the European Medicines Agency 4

The American College of Medical Genetics and Genomics recommends that baseline diagnostic studies for Fabry disease should include ECG, echocardiogram, ophthalmologic examination, renal function tests, and plasma/urine GL-3 4
The Fabry Disease Foundation advises follow-up with a metabolic specialist at 6-month intervals to monitor for onset of symptoms, and construction of a detailed pedigree to identify at-risk family members 4

The National Gaucher Foundation classifies Gaucher disease into three main variants: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic), and notes that management approach varies based on disease type and severity 4

The American College of Medical Genetics and Genomics recommends comprehensive management requiring an ongoing multidisciplinary team approach, including relevant medical specialists familiar with LSDs, to monitor for disease progression and treatment efficacy 2
The Society for Inherited Metabolic Disorders notes that genetic counseling is essential to provide understanding of inheritance patterns and identify at-risk family members 2

The American College of Medical Genetics and Genomics notes that for women with X-linked LSDs like Fabry disease, disease manifestations may be determined by the degree of X-chromosomal inactivation 1
The National Tay-Sachs and Allied Diseases Association reports that carrier screening programs have been effective in reducing incidence of certain LSDs, particularly Tay-Sachs disease in Ashkenazi Jewish populations 1
The American College of Medical Genetics and Genomics recommends patient and parent support groups to provide valuable emotional support and practical advice 2