It is difficult to generalize LSD symptoms. Although the diseases share a common basic pathogenesis, the different types of substrate stored and locations of storage lead to tremendous clinical variability across the LSD category and often even within a single disease.^[1,2] Clinical manifestations tend to be progressive, as more waste substrate accumulates over time.

As a group, LSDs affect nearly every bodily system,^[2] and symptoms can vary in severity from relatively mild somatic manifestations to severe and rapidly progressing neurologic pathologies. Many of the diseases are classified into separate sub-types based on factors such as age of onset, affected organs/systems, and severity. But even those without formal sub-types generally encompass a spectrum of clinical manifestations.^[3]

While no single symptom is an LSD hallmark, several frequently present across enough of the disorders that they can be considered “red flags” to raise a physician’s suspicion and prompt further investigation. LSD symptoms often present in clusters, so the appearance of more than one of these is even more suggestive:^[1,2,3,4]

Coarse facial features	Corneal opacity
Angiokeratoma	Hepatosplenomegaly

Coarse facial features (sometimes with macroglossia)

Corneal clouding or related ocular abnormalities

Angiokeratoma

Umbilical/inguinal hernias

Short stature

Developmental delays

Joint or skeletal deformities

Organomegaly (especially liver and spleen)

Muscle weakness or lack of control (ataxia, seizures, etc.)

Neurologic failure/decline or loss of gained development

Particularly noteworthy are any signs of degenerative process--such as loss of motor skills, increasing dementia or behavioral abnormalities, and muscular or neurologic deterioration--that suggest a progressive disorder.^[2]

For details on each disease’s symptoms, see the disease fact sheets (accessible through the menu at the top right of the page).

The LSDs with neurologic involvement can often be the most severe, marked by rapid decline and high mortality rates.^[5] But generally, predicting LSD progression and outcome is challenging, especially in later-onset patients.^[1]

Often, a single disease is associated with several different gene mutations, which may partly account for the disease’s clinical heterogeneity. Nevertheless, genotype-phenotype correlations are not always consistent; the very same mutation may result in quite different outcomes in different patients.^[2] Other factors can also influence how a disease progresses:^[4] residual enzyme activity (versus complete deficiency); treatment or supportive care (and when in the disease course it is initiated); environmental influences; and unknown genetic factors.

Early identification and diagnosis is essential. Early intervention is especially important for the most serious and debilitating symptoms--particularly neurologic and skeletal--which once established often do not respond to even disease-specific therapies.^[1] For more information on LSD therapies and management, see the Disease Management page.

1. Wenger, DA. Insights into the Diagnosis and Treatment of Lysosomal Storage Diseases. Arch Neurol; 60: 322-328.

2. Wilcox, WR. Lysosomal Storage Disorders: The Need for Better Pediatric Recognition and Comprehensive Care. Journal of Pediatrics; May 2004: S3-S14.

3. Meikle, PJ, et al. Prevalence of Lysosomal Storage Disorders. JAMA; 281: 249-254.

4. Muenzer, J. The Mucopolysaccharidoses: A Heterogeneous Group of Disorders with Variable Pediatric Presentations. Journal of Pediatrics; May 2004: S27-S34.

5. Desnick, RJ, Schuchman, EH. Enzyme Replacement and Enhancement Therapies: Lessons from Lysosomal Storage Disorders. Nature Reviews - Genetics. 2002; 3: 954-966.