I-cell disease

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"ML II" redirects here. For the American activist and philosopher, see Martin Luther King Jr.
I-cell disease
Other namesMucolipidosis II (ML II)
SpecialtyMedical genetics
CausesMutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB)

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II),[1][2] is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to mannose residues on specific proteins. Mannose-6-phosphate serves as a marker for proteins to be targeted to lysosomes within the cell. Without this marker, proteins are instead secreted outside the cell, which is the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances (e.g. oligosaccharides, lipids, and glycosaminoglycans)[3] in various tissues throughout the body (i.e. fibroblasts). As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells" seen microscopically. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood, but they remain inactive at blood pH (around 7.4) because they require the low lysosomal pH 5 to function.

Signs and symptoms

Mucolipidosis II (ML II) is a particularly severe form of ML that has a significant resemblance to another

congestive heart failure
or recurrent respiratory tract infections.

Pathophysiology

I-cell disease is an

lysosomes, the enzymes are erroneously transported from the Golgi to the extracellular space. Consequently, lysosomes lack the requisite hydrolytic enzymes needed for catabolism of cellular debris, so this debris accumulates within them and forms the characteristic intracellular inclusions (hence the name of the disorder).[5] Hydrolases
secreted into the blood stream cause little problem as they are inactivate at the near neutral pH of blood (7.4).

It can be associated with N-acetylglucosamine-1-phosphate transferase (GNPTA).[6] In a case report, I-cell disease was complicated by severe dilative cardiomyopathy (DCM).[7]

Though rare, a deficiency of

glycosaminoglycans
would be present.

Diagnosis

Diagnostic measures can include the following:

Before birth:

In infants:

Treatment

There is no cure for I-cell disease/Mucolipidosis II disease; treatment is limited to controlling or reducing symptoms. Nutritional supplements, particularly

speech therapy to improve language acquisition are treatment options. Surgery can remove the thin layer of corneal clouding to temporarily improve the complication. It is possible that bone marrow transplant may be helpful in delaying or correcting the neurological deterioration that occurs with I-Cell disease.[9] The Yash Gandhi Foundation is a US non-profit organization which funds research for I-Cell disease.[10]

References

  1. ^ "mucolipidosis II" at Dorland's Medical Dictionary
  2. S2CID 20999105
    .
  3. ISBN 9780323053730.{{cite book}}: CS1 maint: multiple names: authors list (link
    )
  4. ISBN 9780071831420
    .
  5. ^
    ISBN 978-0-7817-2265-0
    .
  6. S2CID 24959938
    .
  7. ^ Sahha.gov.mt - 2006 Dec;29_1
  8. ^ a b c d e "I Cell Disease - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2017-11-02.
  9. ^ "Inherited Metabolic Storage Diseases and BMT - MED - PEDS - Blood and Marrow Transplantation Program, University of Minnesota". Archived from the original on 2010-06-20. Retrieved 2009-12-01.
  10. ^ "Yash Gandhi Foundation". Yash Gandhi Foundation. Retrieved 2023-09-25.

External links

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