This article discusses about an inherited condition of the kidneys called Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis. Nephropathic Cystinosis is an autosomal recessive inherited disorder. The disease is caused by accumulation of amino acid cystine within the cells. Intracellular amino acid accumulation causes cellular damage. This usually affects major organs of the body, specifically kidneys and eyes. In this article, we will discuss about the accumulation of cystine affecting the kidneys and the resulting complications from them. The diseases often cause severe symptoms in infant and children.1 This article will discuss the causes, symptoms, and treatment for Nephropathic Cystinosis. Early diagnosis and treatment prevents early fatal complications.2
How Is Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis Defined?
- Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis is a lysosomal storage disease caused by autosomal recessive genetic malfunction.
- Cystinosis is a pathological condition in which there is accumulation of intracellular amino acid cystine, which is a building block for proteins, in the cells.
- Excessive accumulation of cystine results in formation of crystals since cysteine precipitates in cells.
- Cysteine crystal causes damage to the cells. Crystals of cystine affects adversely cellular and tissue function in many organs in the body.
- The vital organs most susceptible to this damage are the kidneys and the eyes.
- Cystinosis primarily affecting the kidneys is known as Nephropathic Cystinosis.
Describe The Cause Of Cystinosis In Infants?
- Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis usually starts in infancy resulting in inadequate growth and a typical form of kidney dysfunction called Fanconi Syndrome.
- Impaired renal tubule function causes Fanconi syndrome.
- Unabsorbed cysteine molecules reabsorbed into blood are instead excreted via urine.
- This in turn can result in loss of vital minerals, salts, and other nutrients from the body.1
- This loss of vital nutrients hinders the growth causing soft bowed bones, especially in legs.
- This nutrient imbalance also causes increased urination, thirst, dehydration, and also acidosis.
- If left untreated, children generally have absolute renal failure by the age of about 10.
Causes of Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Cystinosis is caused as a result of mutations in CTNS gene.
- Mutations in CTNS gene results in deficiency of a protein named Cystinosin.
- Inside the cells, Cystinosin flushes cystine out of lysosomes. When this protein Cystinosin becomes missing as a result of the mutation of the CTNS gene, cystine starts to accumulate in the cells and starts to form crystals.
- This gradual buildup of cystine results in damage to the cells in the kidneys.
What Is The Influence Of Gene Mutation In Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis?
- Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis is usually caused due to the mutation in the CTNS gene resulting in build up of cystine causing Cystinosis.
- Cystine is accumulated because of abnormal restricted cystine transport from lysosome.
- The restriction of cystine transport causes massive intra-lysosomal accumulation of cysteine.
- The over accumulation of cystine interferes with cell function and eventually causes destruction and death of the cells.
Symptoms of Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
All the symptoms and signs of Falconi syndrome are observed. Additional symptoms and signs are as follows-
- Muscle Deterioration
- Inability to Swallow
- Impaired Sweating
- Decreased Hair and Skin Pigmentation
- End Stage Renal Disease
- Low Thyroid Hormone
Tests to Diagnose Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Urine Red Blood Cells are Absent
- Proteinuria- Higher concentration of protein found in urine
- Glycosuria- Higher concentration of carbohydrate found in urine.
- Low Osmolality
- Urine Electrolyte- Sodium, potassium, calcium and chloride excretion are measured.
- Mass Spectrometry- Mass spectrometry test is used to measure the white blood cells cysteine levels.
- Blood Electrolyte Study-Following electrolytes show abnormal levels.
- Hypokalemia level - Low blood potassium level
- Hypophosphatemia- Low serum phosphate level
- Hypernatremia- Low sodium level is observed
- Bicarbonate- Low bicarbonate level is observed.
- pH- acidosis
- Blood Gas Studies-
- Metabolic acidosis is observed.
Examination of Crystal-
- Cystine crystals is examined in alkaline urine. Crystals are hexagonal in shape and colorless. Since crystals are colorless often crystals are examined under polarized background and polarized color inference.
Microbiology Studies for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- White Blood Cells- Cystine levels are examined within polymorphnuclear leukocytes.
- Fibroblast Culture- Cystine levels are measured in cultured fibroblast.
Kidney Biopsy for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Histological examinations of kidney cells are performed to observe intracellular cystine.
Radiological Studies for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Renal Ultrasound Examination- To evaluate kidney stone and size.
- CAT Scan- To evaluate kidney stone and size.
- MRI of the kidney- To evaluate kidney stone and size.
Treatment for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
Symptomatic Treatment For Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- High dosage of vitamin D
- Electrolyte Supplements- Sodium citrate to treat metabolic acidosis
- Electrolyte Replacement- Potassium, bicarbonate and phosphate abnormalities treated with oral or intravenous supplements.
Therapeutic Treatment For Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
Cysteamine For Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Cysteamine is a cystine depleting agent.4
- Cysteamine is the only medication, which has the potential to slow down the progression of cystinosis by removing cystine from cells.
- Cysteamine is a cystine-lowering agent, which depletes cystine levels in cells.
NSAIDs To Treat Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Indomethacin- Reduces diuresis and water loss.
- May cause gastric (stomach) ulcer.
Thyroid Hormone Treatment for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Replace thyroid hormone
Growth HormoneTreatment for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Growth hormone is tried for improvement of growth.
Cysteamine Eye Drops for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- Removes the cystine crystals in the cornea. Symptomatic relief of photophobia may be observed in most of the cases following treatment.
Renal Transplantation for Abderhalden–Kaufmann–Lignac Syndrome or Nephropathic Cystinosis
- End Stage Renal Disease
- Late Diagnosis
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Sfaihi L1, Aloulou H, Ben Amor S, Kamoun T, Hachicha M.
Fetal Pediatr Pathol. 2013 Feb;31(1):66-70.
2. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience.
Greco M1, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F.
Kidney Int. 2012 Jan;81(2):179-89.
Pediatr Nephrol. 2010 Dec;25(12):2459-67.
3. Infantile nephropathic cystinosis presenting as incomplete Fanconi syndrome and refractory rickets.
Rajadurai VS, Shanbag P, Seshadri MS, Khanduri U, Alexander TA, Jadhav MA.
Indian J Pediatr. 1989 May-Jun;56(3):428-35.
4. Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults.
Brodin-Sartorius A1, Tête MJ, Niaudet P, Antignac C, Guest G, Ottolenghi C, Charbit M, Moyse D, Legendre C, Lesavre P, Cochat P, Servais A.
Kidney Int. 2012 Jan;81(2):179-89.