Tests and Services
Therapeutic Monitoring: Monitoring Intracellular Cystine in White Blood Cells (WBC, Leukocytes)
We recommend that WBC cystine be measured just before a dose of cysteeamine, near the "trough" of cysteamine (the time of lowest drug level).
As opposed to CystagonTM
, the absolute trough comes a little later with ProcysbiTM
about a half hour after the dose, but the small difference in WBC cystine is
less of a consideration than the practical concerns about precise timing after a dose, as larger differences could arise if
sampling is delayed.
There are two types of testing available: (1) The older mixed leukocyte test
, which requires immediate preparation but
can permit freezing of samples prior to shipping (note: testing on samples of whole blood shipped directly to other labs are subject to instability [see
Fidler MC, et al., Pediatr Nephrol. 2009 24(12):2465-6
Time before isolating cystinotic leukocytes affects reliability of cystine determination.
, and (2) the newer granulocyte test
, which does not require extra steps
before shipping, but does have critical packaging and shipping requirements.
has kindly set up a program to assist with drawing,
packaging and shipping. See information posted as
Cystinosis Care Team
Procysbi testing guidelines
The simplest method is the granulocyte testing arranged through the TranscendRare program
Traditional method-- Mixed Leukocytes:
This method depends upon isolation of leukocytes immediately after blood drawing. Isolation of leukocytes involves a
series of simple steps, but requires some time.
The stabilized, pelleted leukocytes can be kept frozen for a few days until it is express-mailed to our laboratory.
This method is recommended for samples which are drawn outside the range of next morning express shipping.
In other cases, the granulocyte method is generally preferable, because so much less preparation time is required at the point-of-care.
Details of the method are available here, including full step-by-step process illustration.
Each step is simple, but the intermediate samples cannot be left unattended, so the entire process requires a >2h time commitment.
We can arrange to send kits with materials needed for this preparation; see WBC test kit request form.
In remote regions, where express shipping of frozen samples is not feasible, the pellets may be placed onto standard
bloodspot filter paper, dried thoroughly and shipped at room temperature.
Newer method-- Granulocytes::For this method, whole blood can be sent in a
yellow-top (ACD- solution A) tube, refrigerated (not frozen) and sent by express shipping to
our lab on the same day it is drawn (Monday through Thursday).
Coordinated by the Horizon Rare Disease Unit:
Sample drawing, materials and expenses for shipping, and financial
assistance for the test itself may be covered through their program, making
testing much easier. For information, contact the WBCkit Program.
Independent preparation and shipping of samples:
If the lab is able to draw, prepare and ship the sample independently, it is very
important that these instructions are followed to ensure the integrity of the
sample is maintained:
≥2.0 ml in ACD-Solution A (yellow-top).
Refrigerate within 1 hour of collection. (DO NOT FREEZE)
- SPECIMEN MUST BE SHIPPED THE SAME DAY AS COLLECTION
TO ARRIVE AT OUR LABORATORY THE FOLLOWING MORNING FOR
PROCESSING. PLEASE COLLECT AND SHIP SPECIMENS MONDAY-THURSDAY;
WE ARE CLOSED WEEKENDS AND HOLIDAYS.
- See instructions for packaging shipments here.
- Label the package
"KEEP REFRIGERATED. DO NOT
or place appropriate
safe handling label. failure to do so may result in
the carrier freezing the package in the plane, and as a result
freezing the blood.
- The specimen must be shipped by Fed-Ex Priority Overnight
the same day as sample was collected.
Shipping Address: See contact information.
Packaging materials are illustrated here.
Samples should be accompanied by the
UCSD Biochemical Genetics and
Metabolomics standard requisition form.
Diagnosis of Cystinosis
Diagnosis by White Blood Cells: This is the preferred method. The same procedure as above may be performed, either with
mixed leukocytes or granulocytes.
Diagnosis by DNA: It is useful to define a mutation in the CTNS gene to confirm a diagnosis of cystinosis,
and this may be the method of choice in screening family members or new babies in families where the mutations are known in an
affected relative. To find a testing laboratory, refer to a genetic testing registry, e.g. the GTR (NCBI, www.ncbi.nlm.nih.gov/gtr/).
Diagnosis by Skin Fibroblasts: If circumstances require, cultured cells can be sent for diagnosis in fibroblasts.
Please contnact the lab first in such cases.
Diagnosis by Placenta: Previous work showed that it was possible to make the diagnosis of cystinosis in a newborn
baby in some cases by examination of the placenta. Unfortunately, we have found considerable variation in examination of
placentas, and we are not able to validate the test to the standard we feel is required for clinical testing.
At the same time, DNA testing has become feasible in recent years, and although the question may not be resolved in all
families, it is more reliable to proceed to molecular testing when possible,
or to wait until the newborn baby is a few weeks of age to send routine leukocyte testing to establish the diagnosis.
Prenatal Diagnosis by Amniocytes & Chorionic Villi:
It is possible in principle to diagnose cystinosis prenatally from measurement of intracellular cystine in chorionic villus
or amniocyte cultures, but we have concerns about formal validation of the tests to assure compliance with clinical
laboratory standards. Also, molecular testing using DNA methods has become available (see "Diagnosis by DNA", above)
and generally can provide a definitive answer. Accordingly, we no longer offer prenatal testing.
Heterozygote Carrier Detection by Granulocytes (Polymorphonuclear Leukocytes): There is some overlap between heterozygotes
and control individuals, but in most cases heterozygotes are well discriminated from the control range with granulocyte preparations (see above).