Lysosomal storage disorders

metachromatic leucodystrophy
1. a sulfatidosis
  1. build up of sulphatides causes destruction of myelin
2. diag on testing white cell enzymes
lipid storage disorders (sphingolipidoses)
1. build up of sphingolipids (essential components of CNS membranes)
2. diag on testing white cell enzymes
3. Tay-Sachs disease
  1. hexoaminidase A enzyme defect
  2. clinical features
    1. autosomal recessive disorder
    2. commonest among Ashkenazi Jews
    3. developmental regression in late infancy
    4. exaggerated startle response to noise, visual inattention & social unresponsiveness
    5. severe hypotonia, enlarging head
    6. cherry red spot at macula
    7. death by 2-5 years
    8. diagnosis
      1. measurement of specific enzyme activity
    9. carrier detection of high risk couples is practised
    10. prenatal detection is possible
4. Gaucher disease
  1. beta-glucosidase enzyme defect
  2. occurs in 1 in 500 Ashkenazi Jews
  3. chronic childhood form- splenomegaly, bone marrow suppression, bone involvement, normal IQ
  4. acute infantile form- splenomegaly, neuro degen w/ seizures
  5. splenectomy may alleviate hypersplenism
  6. carrier detection & prenatal diag possible
5. Niemann-Pick disease
  1. sphingomyelinase enzyme defect
  2. 3-4 months old: feeding difficulties & failure to thrive
  3. hepatosplenomegaly, developmental delay, hypotonia & deterioration of hearing and vision
  4. cherry red spot in macula affects 50%
  5. death by 4 years
mucopolysaccharidoses
1. progressive multisys disorders
  1. neuro
  2. ocular
  3. cardiac
  4. skeletal
  5. 5 types
    1. MPS I (Hurler)
      1. autosomal recessive
      2. organs affected
        cornea***
        heart**
        brain***
        skeletal**
    2. MPS II (Hunter)
      1. X-linked inheritance
      2. heart*
      3. brain**
      4. skeletal**
    3. MPS III (Sanfilippo)
      1. autosomal recessive
      2. +/-cornea
      3. brain*
      4. skeletal*
    4. MPS IV (Morquio)
      1. autosomal recessive
      2. cornea***
      3. heart**
      4. skeletal**
  6. clinical features
    1. eyes
      1. corneal clouding
      2. glaucoma
      3. retinal degen
    2. skin
      1. thickened skin
      2. coarse facies
    3. heart
      1. valvular lesions
      2. cardiac failure
    4. neurology
      1. developmental regression
    5. skeletal
      1. thickened skull
      2. broad ribs
      3. claw hand
      4. thoracic kyphosis
      5. lumbar lordosis
    6. Other
      1. hepatosplenomegaly
      2. carpal tunnel syn
      3. conductive deafness
      4. umbilical & inguinal hernias
2. hepatosplenomegaly
3. developmental delay ff period of normal growth & development up to 6-12 months of age
  1. developmental attainment then slows
    1. kids show loss of skills
4. 6 months old: characteristic faces emerge
  1. coarsening of facial features
  2. prominent forehead due to frontal bossing
5. diagnosis
  1. ID enzyme defect
  2. excretion in urine of glycosaminoglycans (GAGs)
6. Rx
  1. supportive
    1. need dependent
  2. bone marrow transplantation to replace enzymes
    1. can't reverse any established neuro abnormality

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Lysosomal storage disorders

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	Created by v.djabatey almost 12 years ago