Skip to main content

Table 1 Summary of general disease characteristics of MLD, MPS II and MPS IIIA

From: Assessing the impact on caregivers caring for patients with rare pediatric lysosomal storage diseases: development of the Caregiver Impact Questionnaire

Disease Types Age of onset Life expectancy Primary symptoms Key similarities/differences within disease types Similarities between MLD, MPS II and MPS IIIA
MLD Late-infantile
(onset before 3 years of age) [2]
Median 1.5 years [3] Mean age at death 4.2 years [4] Motor related (e.g. weakness, gait abnormalities, quadriparesis, dysarthria, hearing difficulties, vision impairment, incontinence) [5]. Motor decline is typical for both late-infantile and juvenile MLD (more rapid in late-infantile); in the juvenile form, it may be preceded by cognitive and behavioral problems [2]. All three diseases tend to have a pediatric onset and are associated with significantly reduced life expectancy.
Juvenile MLD, severe MPS II and MPS IIIA are associated with behavioral problems and eventual motor decline. In late-infantile MLD, patients develop motor deficits very young, making manifestations of behavioral problems difficult to detect.
Juvenile (onset before 16 years of age) [2] Median 6 years [3] Mean age at death 17.4 years [4] Neuropsychiatric or cognitive prodrome (i.e. frontal lobe dysregulation, followed by gradual neurologic decline) [6].
MPS II Severe (neuronopathic) – two-thirds of patients, with signs and symptoms appearing by 3 years of age [7] Median 1.5 years [8] Median age at death 11.7 years [9] Affects multiple organs and physiologic systems (e.g. facial dysmorphism, organomegaly, joint stiffness and contractures, pulmonary dysfunction, myocardial enlargement and valvular dysfunction, and neurologic involvement).
In patients with neurologic involvement, intelligence is impaired [10].
Patients with the severe form of MPS II have cognitive impairment; patients with the less severe form do not experience significant cognitive involvement [9].
Mild (non-neuronopathic) Median age at death 14.1 years [9] Individuals with non-neuronopathic MPS II are of normal intelligence [11].
MPS IIIA NA Mean 3 years [12] Median age at death 15.0 years [12] Primarily characterized by degeneration of the central nervous system, resulting in severe cognitive impairment (e.g. speech delay) as well as hyperactivity and aggressive behavioral problems [13].
Behavioral difficulties tend to become increasingly severe for 5 or 10 years, after which there is a regression in behavioral disturbances, which is associated with a progressive and severe loss of intellectual and motor functioning [13].
Somatic symptoms include coarse facial features and skeletal pathology that affects growth and causes degenerative joint disease, hepatosplenomegaly, macrocrania and hearing loss [13].
The clinical spectrum in MPS IIIA is broad (e.g. patients typically survive until early teens in the most severe cases or as late as the sixth decade in attenuated forms) [13].
  1. MLD metachromatic leukodystrophy, MPS II mucopolysaccharidosis type II, MPS IIIA mucopolysaccharidosis type IIIA, NA not applicable