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Lysosomal Storage Diseases (LSDS)

Lysosomal Storage Diseases (LSDS) are a group of inherited metabolic disorders caused by defects in the function of lysosomes, which are specialized organelles found in cells.

Lysosomes contain enzymes that break down and recycle various cellular waste products, such as complex carbohydrates, lipids, and proteins. In lysosomal storage diseases, the dysfunction of one or more of these enzymes results in the accumulation of undigested or partially digested substances within the lysosome, leading to cellular damage and a wide range of clinical manifestations.

Types of lysosomal storage diseases

There are more than 50 different types of lysosomal storage diseases, each caused by a specific genetic mutation that affects the function of a particular lysosomal enzyme or protein. Some of the more well-known LSDs include.

Gaucher disease

Caused by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in various organs, such as the liver, spleen, and bones.

Fabry disease

Results from a deficiency in the enzyme alpha-galactosidase A, causing a buildup of a fatty substance called globotriaosylceramide in blood vessels, kidneys, heart, and nerves.

Pompe disease

Caused by a deficiency in the enzyme acid alpha-glucosidase, leading to the accumulation of glycogen in muscles and organs, particularly the heart and skeletal muscles.

Niemann-Pick disease

Resulting from defects in the enzymes acid sphingomyelinase (Type A and B) or NPC1/NPC2 proteins (Type C), causing the buildup of sphingomyelin and/or cholesterol in cells.

Mucopolysaccharidoses (MPS)

A group of disorders caused by deficiencies in enzymes that break down complex carbohydrates called glycosaminoglycans, leading to their accumulation in various tissues and organs.

The symptoms and severity of lysosomal storage diseases can vary widely, depending on the specific disorder and the degree of enzyme deficiency. Common clinical manifestations may include organomegaly (enlarged organs), bone abnormalities, neurological impairments, and developmental delays. Treatment options for LSDs may include enzyme replacement therapy, substrate reduction therapy, hematopoietic stem cell transplantation, gene therapy, and supportive care to manage symptoms and complications

How newborn Screening helps LSDS

Newborn screening for Lysosomal Storage Diseases (LSDS) is crucial for timely intervention and better clinical outcomes. Several strategies and diagnostic tools can be employed to facilitate early detection of these disorders:

Newborn screening

Some LSDs, like Pompe disease and Fabry disease, are included in newborn screening programs in certain regions. These screening tests typically analyze dried blood spot samples from newborns to detect enzyme deficiencies or specific biomarkers associated with LSDs.

Family history and genetic counseling

If there is a known family history of LSDs, at-risk individuals can undergo genetic counseling and testing to determine their carrier status or to diagnose affected individuals. Prenatal testing or pre-implantation genetic diagnosis (PGD) may also be considered for couples with a known risk of having a child with an LSD.

Clinical suspicion

Healthcare providers should consider the possibility of an LSD in patients presenting with unexplained symptoms consistent with these disorders, such as organomegaly, developmental delays, neurological deficits, or bone abnormalities. A high index of suspicion and early referral to a specialist can facilitate prompt diagnosis.

Enzyme assays

Blood, tissue, or cultured cell samples can be tested to measure the activity of specific lysosomal enzymes. Reduced enzyme activity can indicate the presence of an LSD, although further confirmatory testing is usually required.

Molecular genetic testing

Genetic testing can be performed to identify the specific gene mutations responsible for an LSD. This is particularly useful for confirming a diagnosis, determining the severity of the disease, and providing information for family planning and genetic counseling.

Imaging studies

Radiologic imaging, such as X-rays, MRI, or CT scans, can help identify characteristic abnormalities associated with certain LSDs, such as bone deformities or organ enlargement. These findings can support the clinical suspicion of an LSD and guide further diagnostic testing.

Histopathology and electron microscopy

Tissue biopsies from affected organs can be analyzed under a microscope to identify the presence of storage material, which is characteristic of LSDs. Electron microscopy can provide further details about the nature of the accumulated substances, helping to narrow down the diagnosis.

Biomarker analysis

Some LSDs have specific biomarkers that can be measured in blood, urine, or other biological samples. The presence or elevated levels of these biomarkers can suggest an LSD and guide further diagnostic testing.

A combination of these diagnostic approaches, guided by clinical suspicion and the patient’s medical history, can help facilitate the early diagnosis of lysosomal storage diseases and enable prompt initiation of treatment and management strategies.

Why early diagnosis of LSDS

Early diagnosis of lysosomal storage diseases (LSDs) is crucial for several reasons, as it can significantly impact the affected individual’s health, quality of life, and long-term outcomes

Timely treatment initiation

Early diagnosis allows for the prompt initiation of appropriate treatments, such as enzyme replacement therapy, substrate reduction therapy, hematopoietic stem cell transplantation, or gene therapy. Starting treatment early can help slow disease progression, alleviate symptoms, and improve overall prognosis.

Improved symptom management

Early intervention can help better manage symptoms and prevent or minimize complications associated with LSDs, such as organ damage, neurological impairment, and skeletal deformities. This can lead to a better quality of life for affected individuals.

Enhanced growth and development

By minimizing the impact of the disease and associated complications, early diagnosis and intervention can help promote better overall growth and development in children with LSDs, leading to improved physical, cognitive, and emotional outcomes.

Informed family planning

Early diagnosis of an LSD in a family member can provide valuable information for family planning, allowing for informed decisions regarding future pregnancies. Genetic counseling can help families understand the inheritance pattern, discuss reproductive options, and provide guidance on prenatal testing or pre-implantation genetic diagnosis.

Psychosocial support

Early diagnosis can help families access essential psychosocial support services to cope with the challenges associated with having a child with an LSD. This includes connecting with support groups, mental health professionals, and educational resources to better understand and manage the condition.

Personalized care and monitoring

Early diagnosis enables healthcare providers to develop a personalized care plan and closely monitor the affected individual’s health, adjusting treatment and management strategies as needed to optimize outcomes and minimize complications.

Contribution to research

Identifying individuals with LSDs early can help researchers study the natural history of these diseases, evaluate the effectiveness of various treatment options, and develop new therapeutic approaches. This can ultimately contribute to improving the care and outcomes for individuals with lysosomal storage diseases.

The available in-depth levels


The StepOne® panel includes Inherited Metabolic Disorders caused by the missed synthesis of important enzymes or the inability to use substances that are essential for life. Currently, only a few diseases are included in a mandatory neonatal screening in some Countries (for instance, in Italy they are only three: phenylketonuria, congenital hypothyroidism, and cystic fibrosis). Bioscience Institute’s expanded metabolic screening allows for the timely detection of  up to 55 diseases.


Parents can ask the Bioscience Institute for a more in-depth level of investigation in order to examine the presence of two more categories of pathologies: Severe Combined ImmunoDeficiency (SCID) and Lysosomal Storage Diseases (LSDs).

SCID (Severe Combined ImmunoDeficiency)

SCID comprises a group of diseases (caused by at least 13 genetic defects) in which the immune system is severely compromised, to the point that the body is unable to defend itself against infectious agents. They generally manifest from the first months of life,  with recurrent infections characterized by a particularly aggressive course.

LSDs (Lysosomal Storage Diseases)

Lysosomal storage diseases are caused by an alteration of any of the functions of lysosomes (organelles responsible for the degradation and the recycling of cell metabolism products). In particular, they are associated with the deficiency or the malfunctioning of the enzymes responsible for their activity.

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