Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (423 page)

   Deletion/duplication analysis—is recommended when mutations were not found by sequence analysis. There are known cases of complete deletion and of partial deletions in ASPA gene.

Suggested Reading

Matalon R, Michals-Matalon K. Canavan disease. In: Pagon RA, Adam MP, Bird TD, et al., eds.
GeneReviews
^™
[Internet]
. Seattle, WA: University of Washington, Seattle; 1999:1993–2013 [Updated 2011 Aug 11]. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK1234/

CYSTINOSIS (CYSTINOSIS, NEPHROPATHIC; CTNS)

MIM #219800

   Definition

Cystinosis is an autosomal recessive inherited disease caused by impaired transport of cystine from lysosomes to cytoplasm that results in intralysosomal accumulation of cystine. There are three clinical forms of cystinosis: infantile (nephropathic) cystinosis; late-onset cystinosis; and benign cystinosis.

   Who Should Be Suspected?

Infantile cystinosis is the most severe and the most common type of cystinosis. Children with nephropathic cystinosis appear normal at birth, but by 9–10 months of age, have symptoms that include excessive thirst and urination and failure to thrive. The abnormally high loss of phosphorus in the urine leads to rickets. The longer-term manifestations of cystinosis, primarily in older patients and as a result of renal transplantation, include pancreatic endocrine and exocrine insufficiency, and recurrent corneal erosions, CNS involvement, and severe myopathy.

   Relevant Tests and Diagnostic Values

   Cystine measurement in blood cells, amniotic fluid cells, and chorionic villi.

   Sequence analysis of the
CTNS
gene (chr17p13.2) is clinically available; >50 mutations have been identified. However, in approximately 20% of patients, no mutation is identified.

   FISH analysis detects a relatively common 57 kb deletion in the
CTNS
gene.

   Other Considerations

   Kidney biopsy can demonstrate cystine crystals and destructive changes to the kidney cells and structures.

Suggested Reading

Bendavid C, Kleta R, Long R, et al. FISH diagnosis of the common 57 kb deletion in CTNS causing cystinosis.
Hum Genet.
2004;115:510–514.

FABRY DISEASE (ANGIOKERATOMA CORPORIS DIFFUSUM, ANDERSON-FABRY DISEASE)

MIM #301500

   Definition

Fabry disease is a rare X-linked recessive lysosomal storage disease caused by a deficiency of α-galactosidase A (α-gal A) that results in progressive accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in plasma and vascular endothelium. This glycosphingolipid accumulation leads to ischemia and infarction in various organs (e.g., kidney, heart, brain, eye, nerves). Characteristic findings include angiokeratomas of skin and a whorl-like corneal pattern of cream-colored lines. Heterozygous females are not just carriers, and they may have mild or severe disease.

   Relevant Tests and Diagnostic Value