Table 2.

Description of the signs and symptoms, and the course of included LSD

LSD	Signs and symptoms	Course of the disease
FD	Main symptoms at onset: fatigue, pain, fever crisis, digestive discomfort, heat stroke, pain in the extremities, foam in the urine, etc Early presence of symptoms in paediatric age	Shortened life expectancy and a significant loss of quality of life FD progression in target organs such as heart or kidneys, such as kidney failure, cardiomyopathy, and cerebrovascular ischemic events (stroke) with irreversible consequences for the patient
GD	The most common sign is a swollen spleen, which can be followed by bone disease and brain involvement and other problems such as tiredness, bleeding, bruising, and lung disease Pain due to bone or neuronal involvement is the most common reason for consultation Thrombocytopenia and anemia	Degenerative disease that can progress to increased visceromegaly (hepatomegaly and splenomegaly), recurrent bone pain, and lung involvement
PD	Symptoms little visible at onset with low impact on quality of life initially The first symptoms are: muscle weakness and difficulty walking, breathing problems and infections of the respiratory system and failure to gain weight and growth at the expected rate. HyperCKemias	Muscle weakness (which can make it very difficult to walk), and breathing problems, that will finally lead to the use of walking aids and mechanical ventilation
MPSI	In the first years of life, patients present visible musculoskeletal alterations of varying degree, as well as corneal opacity	Very disabling degenerative disease that affects children in its most serious forms High impact on quality of life due to physical limitations and cardiovascular and respiratory complications

These four LSD have a wide range of clinical presentation and different phenotypes exists

FD: Fabry disease; GD: Gaucher disease; PD: Pompe disease; MPSI: mucopolysaccharidosis type 1