With cystinosis, “cystin-” refers to cystine, an amino acid, and “-osis” implies disease.
So, cystinosis is a rare condition caused by mutations of the CTNS gene that leads to
a cystine buildup in the body. especially the kidneys and eyes. This can cause tissue
damage, especially in the kidneys and eyes.
Cystine is an amino acid that comes from our diet. When food travels through the stomach
and intestines, the proteins within, are broken down into tiny fragments, called oligopeptides,
or small strings of amino acids. Turnover of muscle, bone and other parts of the body
provide another source of protein that can be broken down into oligopeptides. Many of
these oligopeptides end up in specialized vesicles, called lysosomes, found inside all
of our cells. called lysosomes all over our bodies. Here, they are further broken up into
amino acids like cystine. Now, cystine, like any other amino acid has to leave the lysosome,
and it does this with the help of a specific protein. Generally, genes tell our bodies
how to make proteins. So, the CTNS gene encodes for the protein cystinosin, a transporter
that is found embedded in the lysosomal membrane. Its function is to export cystine out of the
lysosome.
Now, in cystinosis, any one of over 100 mutations can affect the CTNS gene, leading to a defective
cystine transporter. Without a working transporter, cystine has no way of leaving the lysosome,
so it accumulates, turning into cystine crystals in the process. Crystals that slowly damage
organs like the kidneys and eyes.
The mutations that cause cystinosis are inherited in an autosomal recessive fashion, so two
people have to be at least carriers of the mutated CTNS gene, to pass on the condition.
There is a 25% chance that both people will pass down their own CTNS mutation to the offspring.
Only when two mutated CTNS genes are passed is the condition usually expressed.
In general, humans have two copies of their genes, so both must be damaged for there to
be so little cystine transport that cystinosis occurs. That means that a person with cystinosis
must receive a mutated CTNS gene from both the mother and father. For each such mating,
there is a 25% chance that both parents will pass down their own CTNS mutation to the offspring.
Now, depending on the CTNS gene mutation, three types of cystinosis can develop that
differ in the age of onset and severity of symptoms. They are nephropathic, or infantile,
late onset, and ocular. Nephropathic, or infantile cystinosis, is the most common and most severe
form of cystinosis. In this disease, the kidneys are affected, and the infants develop Fanconi
syndrome, a condition, where minerals and nutrients are not absorbed, but instead, are
excreted in the urine. So, some of the symptoms are linked to the kidneys like excessive thirst,
excessive urination, electrolyte imbalances, vomiting, and dehydration with or without
fever. Other symptoms include the failure to thrive, cystine crystals in the cornea,
and elevated cystine levels in white blood cells. There’s also late onset, adolescent,
or intermediate cystinosis where the symptoms of nephropathic cystinosis appear later in
life, around 8 to 20 years of age. Lastly, ocular cystinosis, it usually affects adults
during middle age. Here, the eyes are affected, and the kidneys are spared. Without treatment,
people eventually develop photophobia due to cystine crystal accumulation in the eyes.
We are coming to realize that there is a spectrum of severity in cystinosis and the 3 subtypes
can be difficult to differentiate.
A diagnosis of cystinosis is based upon identification of characteristic symptoms, a detailed patient
history, a thorough clinical evaluation and a variety of specialized tests. The specialized
test includes measuring cystine levels in certain white blood cells, and molecular genetic
testing.
The treatment of cystinosis is directed toward the specific symptoms that are apparent in
each person. But overall, cysteamine, a cystine-depleting agent, is the first-line treatment for cystinosis.
All right, as a quick recap, cystinosis is a rare condition caused by mutations of the
CTNS gene that leads to a cystine buildup in the body, especially causing damage to
organs like the kidneys and eyes. The CTNS gene encodes for the protein cystinosin, a
transporter that is found embedded in the lysosomal membrane. Its function is to export
cystine out of the lysosome. Three types of cystinosis can develop; nephropathic, or infantile,
late onset, and ocular. Nephropathic cystinosis is the most common and severe, and ocular
cystinosis only affects the eyes. It’s diagnosed with specialized tests like measuring cystine
levels in certain white blood cells, and molecular genetic testing. And it’s treated with cysteamine,
a cystine-depleting agent.