Cystinosis is a rare autosomal recessive disorder caused by the impaired transport of the amino acid, cystine, out of cellular lysosomes leading to its excess buildup. It usually appears in children of very young age and infants, the incidence of this disease is 1 in 100,000 live births and the occurrence of this disease, even if so rare, has detrimental effects and lasts lifelong.
What is cystinosis?
In 1931, Fanconi was the first to perceive that cystinosis is associated with urinary wasting of substances such as glucose, amino acids, uric acid, phosphate, and bicarbonate, that are normally reabsorbed during their passage through the renal tubules, which was then named to be Fanconi’s syndrome.
Fanconi’s syndrome mainly affects the function of the proximal convoluted tubule, which is the first part of the tubule that processes the filtrate after passing through the glomerulus. The proximal convoluted tubule abbreviated as the PCT is the most important part of the nephron that helps in the process of reabsorbing the nutrients which a patient suffering from fanconi’s syndrome fails to do.
Cystinosis is an inherited disease ( it is passed down from one generation to the next ), a recessive genetic disorder that requires the patient to have received an abnormal copy of the cystinosin gene, known as the CTNS ( cystinosin, lysosomal cystine transporter ) gene, from both parents. This gene is present on chromosome 17 and encodes a seven-transmembrane domain protein that functions to transport cystine out of lysosomes. Its activity is driven by the H+ electrochemical gradient of the lysosomal membrane. Mutations in this gene cause cystinosis, a lysosomal storage disorder.
Cystinosis not only affects the kidneys but also affects other parts of the body like the eyes, muscles, brain, heart, white blood cells, thyroid and even the pancreas, but causes serious problems to the kidneys.
There are a few types of cystinosis:
– Early-onset ( infantile ) cystinosis
– Late-childhood or adolescent cystinosis
– Adult cystinosis
Nephropathic cystinosis usually is a symptom of early-onset ( infantile ) cystinosis, where the fanconi syndrome as mentioned earlier also simultaneously has an effect by causing the kidneys to be unable to absorb nutrients and minerals such as sodium and potassium, which therefore results in the loss of these essential nutrients in urine. When the infants move on to become children, they are more prone to worsening kidney disease and even develop kidney failure by the time they become 10-12 years in age!
Diagnosing nephropathic cystinosis includes physical exams, checking personal and family medical histories or even a genetic test can also be used to confirm a diagnosis. There are two tests that are done for checking the kidney function:
ACR test that stands for albumin-to-creatinine ratio. Albumin is a protein if present for over 3 months is a sign for kidney disease. Albumin is a protein that keeps fluid from leaking out of your blood vessels into other tissues, it is normally found in the blood but small amounts leak into the urine when the kidneys are damaged.
Blood test to estimate GFR ( glomerular filtration rate ). It is used to check for the creatine ( a waste product from muscle tissues ) level, which is used to calculate the GFR using a math formula. eGFR of 90 or higher is in the normal range, eGFR of 60 - 89 may mean early kidney disease, eGFR of 15 - 59 may mean kidney disease, and eGFR below 15 may mean kidney failure. ( eGFR stand for estimated glomerular filtration rate )
Sourced from: https://www.kidney.org/atoz/content/gfr
Are there treatments available to cure nephropathic cystinosis?
Unfortunately there are no permanent fixes to this disease but there are methods to delay the disruption of the kidneys!
Infants and young children would eventually need to get a kidney transplant, but there are medications, such as procysbi, cystagon, and cysteamine, that can help lower the cystine concentration in the body which can improve symptoms but again not be able to cure the disease as Nephropathic cystinosis is a genetic disorder.
Research is being done and there are many ongoing trials to find a cure to this extreme disease and hopefully they will be successful, after more than about 100 years of the existence of this disease!
Look into the article attached below to quench your curiosity on infantile nephropathic cystinosis!
The link to the article: https://www.kidney-international.org/article/S0085-2538(15)53065-2/pdf
Written by: Siri Kota
Glossary
Nephron: a small unit present in the kidney that helps in the process of filtration of the blood. Each kidney approximately has a million nephrons.
Glomerulus:the filtering unit of the kidney and is composed of a network of capillaries and highly differentiated epithelial cells
Seven-transmembrane domain protein: integral membrane proteins that contain seven membrane-spanning helices. As the name suggests they are coupled to heterotrimeric G proteins on the intracellular side of the membrane.
Lysosomes: a membrane-bound cell organelle that contains digestive enzymes.
Bibliography
“Nephropathic Cystinosis.” National Kidney Foundation, 11 June 2020, https://www.kidney.org/atoz/content/nephropathic-cystinosis.
W;, Nesterova G;Gahl. “Nephropathic Cystinosis: Late Complications of a Multisystemic Disease.” Pediatric Nephrology (Berlin, Germany), U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/18008091/.
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