Schindler's disease, also known as Kanzaki disease or alpha-N-acetylgalactosaminidase deficiency, is a rare lysosomal storage disorder caused by a deficiency of the enzyme alpha-NAGA. This enzyme deficiency leads to an accumulation of glycosphingolipids in the body's cells and tissues. There are three main types which vary in symptoms and age of onset, from a severe early childhood type 1 to a milder adult-onset type 2. The disease has no cure but researchers are investigating enzyme replacement therapy, gene therapy, and bone marrow transplants.

1. SCINDLER’S DISEASE
BY PROFESSOR
KAVAN VYAS Dr. Tymchenko Svetlana
203 department of physiology
Crimean federal university

2. PLAN OF DESCRIPTION
 WHAT IS SCHINDLER’S DISEASE
 SYNONYMS
 CAUSES & REASON
 TYPE OF DISEASE
 SYMPTOMS
 DIAGNOSIS
 TRAETMENT

3.  Lysosomal storage diseases (LSDs) are a group of
approximately 50 rare inherited metabolic disorders
that result from defects in lysosomal function.
 Lysosomes are sacs of enzymes within cells that
digest large molecules and pass the fragments on to
other parts of the cell for recycling. This process
requires several critical enzymes. If one of these
enzymes is defective, because of a mutation, the large
molecules accumulate within the cell, eventually killing
it.
What are lysosomal storage
disorders?

4. What is schindler’s disease?
 Schindler disease, also known as Kanzaki disease and alpha-N-
acetylgalactosaminidase deficiency, it is a rare disease found
in humans which is caused by a deficiency in the enzyme
alpha-NAGA (alpha-N- acetylgalactosaminidase).
 This is lysosomal storage disorder.

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 A deficiency of the alpha-NAGA enzyme leads to an
accumulation of glycosphingolipids throughout the body.
 This accumulation of sugars gives rise to the clinical features

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Location of NAGA gene
 22q13.2 Schindler disease, type III
 22q13.2 Schindler disease, type I
(on 22nd chromosome and q stands for long arm of the chromosome )
( while 13 is for band and 2 stands for sub band)
Schindler disease is an autosomal recessive disorder, so that one an abnormal
allele from both parents in order to have the disease.

7. Other names of schindler’s disease
 alpha-galactosidase B deficiency
 alpha- galNAc deficiency
 alpha N-acetylgalactosaminidase deficiency
 alpha-NAGA deficiency
 angiokeratome corporis diffusum- glycopeptiduria
 GALB deficiency
 Kanzaki disease
 lysosomal glycoaminoacid storage disease -
 NAGA deficiency
 neuroaxonal dystrophy, Schindler type 1
 neuronal axonal dystrophy, Schindler type

8. Cause of Scindler’s disease
 Schindler disease is caused by loss-of-function mutations in NAGA,
a gene encoding a lysosomal exoglycosidase enzyme called α-N-
acetylgalactosaminidase (α-NAGAL) that cleaves terminal α-N-
acetylgalactosamine (GalNAc) residues from glycopeptides and
glycolipids.
 N- Acetylgalactosamine is necessary for intercellular
communication, and is concentrated in sensory nerve structures
 absent activity of the enzyme leads to the abnormal accumulation of
certain complex compounds (glycosphingolipids, glycoproteins, and
oligosaccharides) in certain tissues of the body and in urine

9. Types of schindler’s disease
 There are mainly 3 types of schindler’s disease
 Type 1
 Type 2 OR kanzaki disease
 Type 3
 The classification is based on the the age when patient shows
symtoms of the disease, apart this… slight difference is also
present in symptoms among these 3 types.

10. Type 1 disease
 Schindler disease type I - also called infantile type is the most
severe form. Babies with Schindler disease type I appear
healthy at birth, but at age 8 to 15 months they stop
developing new skills and begin losing skills they have already
acquired.
 These children develop , seizures and eventually lose
awareness of their surrounds.

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 Hearing and visual impairments occurs , low muscle tone and
weakness , even sometimes complete muscle rigidity occurs.
involuntary muscle spasms that result in slow, stiff movements
(spasticity)
 misalignment of the eyes (strabismus) involuntary, rapid eye
movements (nystagmus) and visual impairment due to the
gradual deterioration of the nerves of the eyes (optic atrophy)
leads to blindness.

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 Children with this form of the disease do not usually live past early
childhood.

13. Type 2 disease
 Schindler disease type II or Kanzaki disease occurs In the
adult-onset form
 symptoms may not appear until the second or third decade of
life. A distinctive symptom of Schindler disease type II is
involvement of small blood vessels (telangiectasia) in the skin
that cause reddish small skin lesions, and an increase of its
layer stratum corneum (hyperkeratosis) referred to as
angiokeratomas.

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 Angiokeratomas may first be restricted to a single area
(localized), such as the lower torso, and then appear later in
additional locations (e.g., from the lower torso to the chest
area). These reddish lesions may be flat or raised and vary in
colour, and may occur in clusters. Affected individuals may
also have these lesions in other areas of the body such as the
mucous membranes including the mouth and eyes.

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 The dilation of small lymph vessels may lead to swelling
(lymphedema) particularly of the lower extremities.
 Individuals have also mild intellectual impairment, but do not
show the serious neurological complications associated with
Schindler disease type I.

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 Additional symptoms have been reported in the medical
literature including vertigo, hearing loss, ringing in the ears
(tinnitus), and muscle weakness , experiences pain crises.
 Complication in development of central and peripheral nerve
occurs.

18.  Individuals may also develop distinctive facial features
including mildly coarse features, thick lips, a depressed nasal
bridge and an enlarged tip of the nose.

19. Type 3 disease
 Schindler disease type III, is an intermediate form the disorder.
 Symptoms can range from more serious intellectual
impairment, neurological dysfunction.
 seizures to milder neurological and psychiatric issues such as
speech and language delays and mild autism-like symptoms.

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 Behaviour problem and mental retardation occurs.
 Type 3 disease is less severe than type 1 disease but more
severe than type 2 disease.

22. Histological Changes during
schindler’s disease
 symptoms of type I Schindler disease are associated with characteristic
swellings at the end of nerve fibers (axons). These swellings may be
referred to as dystrophic axonal swellings or “spheroids”.
 The spheroids are characteristic of a neuroaxonal dystrophy – a severe
alteration of nerve cells. These swellings appear to disrupt proper nerve
function by blocking the transmission of impulses between nerve cells.
 apart this demyelinization occurs.

23. Frequency of disease
 Schindler’s disease is very rare.
 Till now only 12 cases from 8 different families are known of this disease.
 Another reason is misdiagnosis and unrecognized.

24. Diagnosis
 detailed patient history
 Urinary analysis (e.g. oligosaccharide and glycopeptide levels)
 Reduced activity of the alpha-NAGA enzyme may be confirmed by
conducting enzyme tests (assays) on cultured white blood cells
(leukocytes), blood plasma, and/or certain skin cells (fibroblasts) from
affected individuals.
 samples of tissue biopsy especially in type 1 disease.
 magnetic resonance imaging (MRI) and
 computer-assisted tomography (CAT) of the brain

25. Treatment
 There is no specific treatment known for schindler’s disease but as a part
of developing medical science , researchers hopefully succeed in some
cases.
 enzyme replacement therapy to compensate for endogenous deficiency.
 Gene therapy
 bone marrow transplants