Lysosomal Storage Disorders Flashcards
What is another name for MPS II?
Hunter Syndrome
What enzyme is deficient in MPS II?
Iduronate-2-sulfatase (I2S)
What is the disease mechanism of MPS II?
Accumulation of GAGs
– Direct cellular disease and organ dysfunction
– Cytokine response
What are signs and symptoms of MPS II?
CNS:
Hydrocephalus
Atlanto-axial instability
Cervical cord compression
Myelopathy
Seizures
Severe behaviour problems
Sleep disturbance
Mental retardation
Appearance:
Coarse facies
Eyes:
Glaucoma
Retinal dystrophy
Ears:
Recurrent otitis media
Sensorineural deafness
Dental:
Caries
Dental abscesses
Respiratory:
Upper airway obstruction
Obstructive sleep apnea
Restrictive lung disease
Frequent infections
Restrictive airway disease
Skeletal:
Degenerative hip dysplasia
Kyphosis or
Kyphoscoliosis
gibbus
Joint contractures
Genu valgum deformities
Gastrointestinal:
Hepatosplenomegaly
Umbilical & inguinal hernia
Swallowing problems
Diarrhea
Drooling
Peripheral nervous system:
Peripheral nerve entrapment
(eg, carpal tunnel syndrome)
Cardiac:
Cardiomyopathy
Dysplastic valves
How is MPS II diagnosed?
- Clinical Signs and Symptoms
- Urinary GAG Excretion
- Iduronate-2-sulfatase (I2S)
activity in blood (leukocytes,
fibroblasts, or plasma) - Exclusion of alternative diagnosis
(ie: multiple sulfatase deficiency) - Molecular Testing
(also mother and mother’s family) - Genetic counseling
- Prenatal diagnostics available
(Chorionic villi or amniocentesis) - Newborn Screening
True or False: Measuring iduronate-2-sulfatase activity is sufficient to
confirm a diagnosis of MPS II in an infant evaluated for an abnormal
newborn screen.
False
What is a pseudodeficiency?
A benign genetic variant that causes the enzyme to appear low in laboratory testing, but it does not cause disease.
How do we distinguish pseudo deficiency from a true enzyme
deficiency?
- Pseudo deficiency does NOT cause substrate accumulation. True enzyme deficiency does.
- Pseudo deficiency variants are relatively common among the general population because they are benign
What is overall management of disease for Hunter Syndrome?
- Enzyme Replacement Therapy
– Idursulfase; idursulfase beta - Hematopoietic Stem Cell Transplantation (HSCT)
- Disease monitoring and supportive
interventions
Acid sphingomyelinase deficiency (ASMD) (Niemann-Pick disease)
Gene: SMPD1
Inheritance: AR
Deficient acid sphingomyelinase (ASM) activity leads to intracellular accumulation of sphingomyelin, a ubiquitous and integral component of the cellular membrane of all cells, in
various cells of the body, which may result in damage to major organs
What are the clinical characteristics of Infantile Onset Pompe Disease?
Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of
four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency.
What are the clinical characteristics of Late-Onset Pompe Disease?
- Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is
characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon
What is surveillance for Pompe Disease?
- Twice-yearly clinical review of development, clinical status, growth, and use of adaptive equipment
- Assessment of respiratory status (CXR, PFTs, Sleep Studies)
- Developmental therapies
- Nutritional and feeding assessments
- Annual renal function studies
- Regular cardiac monitoring (interventions as needed)
– Cardiac Muscle, Electrical Conduction, and Arteriopathy - Annual hearing evaluation
