Download Schindler Disease - Great Ormond Street Hospital Laboratory

Schindler Disease
Contact details
Molecular Genetics Service
Level 6, Barclay House
37 Queen Square
London, WC1N 3BH
T +44 (0) 20 7762 6888
F +44 (0) 20 7813 8578
Samples required

5ml venous blood in plastic EDTA
bottles (>1ml from neonates)

Prenatal testing must be arranged
in advance, through a Clinical
Genetics department if possible.

Amniotic fluid or CV samples
should be sent to Cytogenetics for
dissecting and culturing, with
instructions to forward the sample
to the Regional Molecular Genetics
laboratory for analysis

A completed DNA request card
should accompany all samples
Introduction
Schindler disease (MIM 609241) is a rare autosomal recessive lysosomal storage
disease, which is caused by a deficiency of the enzyme, alpha-Nacetylgalactosaminidase (NAGA). NAGA is a lysosomal glycohydrolase that cleaves
alpha-N-acetylgalactosaminidase moieties from glycoconjugates inside lysosomes.
Schindler disease is clinically heterogeneous with 3 main phenotypes; type 1 is an
infantile-onset neuroaxonal dystrophy; type 2, also known as Kanzaki disease (MIM
609242), is an adult onset disorder characterised by angiokeratoma corporis diffusum
and mild intellectual impairment; and type 3 is an intermediate disorder with mild to
moderate neurological manifestations.
Affected patients have an abnormal urinary oligosaccharide and glycopeptide profile
and the diagnosis is confirmed by a deficiency of the NAGA enzyme in plasma,
leucocytes, or fibroblasts.
The NAGA gene is located on chromosome 22q13.2 and consists of 9 exons, and
family specific mutations are found throughout the gene. To date, 14 patients from ten
families are known and ethnic specific mutations are recognised, information
regarding ethnic origin is therefore a useful indicator.
Referrals

Clinically affected patients should have their diagnosis confirmed by biochemical
analysis; this should be arranged either locally or with the Enzyme Unit, Great
Ormond Street Hospital; (tel: 0207 4059200 ext 1785/6751). Such patients may
then be referred for mutation analysis. If the necessary patient samples are
unavailable genetic testing can be undertaken in the parents of the affected child.

Carrier testing can be offered to the adult relatives of affected patients once a
disease causing mutation has been identified.
Patient details
To facilitate accurate testing and
reporting please provide patient
demographic details (full name, date of
birth, address and ethnic origin), details
of any relevant family history and full
contact details for the referring clinician
Prenatal testing
Prenatal testing is available for families in whom mutations have been identified or in
whom appropriate family studies have been undertaken – please contact the
laboratory to discuss.
Service offered
Mutation screening of exons 1 to 9 by Sanger sequencing analysis. Mutation specific
testing for previously identified family mutations is also available by Sanger
sequencing.
Target reporting time
8 weeks for routine mutation screen in index case. 2 weeks for carrier testing using
mutation specific tests. Please contact the laboratory for urgent cases.
Version 7