• Information
  1. Mucolipidosis II
  2. Combined Deficiency of Factors V and VIII
  3. Hermansky-Pudlak Syndrome
  4. Chediak-Higashi Syndrome
  5. Oculocerbrorenal Syndrome
  6. Griscelli's Syndrome
  7. Usher's Syndrome Type 1B
  8. Choroidermia
  9. X-Linked Non-Specific Mental Retardation

A. Mucolipidosis II

1. Also called inclusion cell disease
2. Autosomal recessive
3. Mutation in N-acetylglucosamine-1-phosphotransferase
4. Leakage of lysosomal hydrolases from cells
   1. Due to lack of mannose-6-phosphate targeting signal
   2. Lysosomal accumulation of undegraded macromolecules

B. Combined Deficiency of Factors V and VIII

1. Autosomal recessive
2. Mutation in mannose-binding lectin (ERGIC-53)
   1. This lectin cycles between endoplasmic reticulum and Golgi apparatus
   2. ERGIC-53 mutation leads to disturbed sorting in endoplasmic reticulum
   3. Involved in transport of Factor V and VIII
3. Clinical coagulopathy - bleeding syndrome

C. Hermansky-Pudlak Syndrome

1. Autosomal recessive
2. Mutation in AP-3 adaptor protein ß3A subunit or HPS1
   1. Defective genesis of lysosomes or related organelles
   2. Leakage of lysosomal membrane proteins to cell surface

D. Chediak-Higashi Syndrome [2]

1. Autosomal recessive
2. Defect in lysosomal trafficking regulator protein
3. Manifest primarily as Neutrophil dysfunction
   1. Problem with degranulation and motility
   2. Thus, PMNs typically have extremely large azurophilic (lysosomal) granules
4. Recurrent pyogenic infections, especially S. aureus and periodontal disease
5. Nystagmus and progressive peripheral neuropathy

E. Oculocerbrorenal Syndrome

1. X-linked
2. Mutation in OCRL-1, an inositol polyphosphate 5-phosphatase
   1. Abnormal secretion of lysosomal hydrolases
   2. Accumulation of phosphatidylinsoitol 4,5-bisphosphate

F. Griscelli's Syndrome

1. Autosomal recessive
2. Mutaiton in myosin-Va
3. Similar to Chediak-Higashi Syndrome

G. Usher's Syndrome Type 1B

1. Autosomal recessive
2. Mutation in Myosin-VIIa
3. Degeneration of retinal and cochlear sensory cells
4. Mouse model is called Shaker-1

H. Choroidermia

1. X-linked
2. Mutation in Rab escort protein 1
3. Defects
   1. Degeneration of retinal pigment epithelium, choroid, photoreceptor
   2. Defective lipid modification of Rab guanosine triphosphatases

I. X-Linked Non-Specific Mental Retardation

1. X-linked
2. Mutation in Rab GDP-Dissociation Inhibitor
   1. Defective recycling and membrane targeting of Rab guanosine triphosphatases
   2. Minor alterations in neuronal development

References

1. Olkkonen VM and Ikonen E. 2000. NEJM. 343(15):1095
2. Lekstrom-Himes JA and Gallin JI. 2000. NEJM. 343(23):1703