Abderhalden–Kaufmann–Lignac syndrome

Overview

Abderhalden–Kaufmann–Lignac syndrome is a rare inherited metabolic disorder classified under the group of lysosomal storage diseases. It is a form of infantile nephropathic cystinosis, a condition caused by the accumulation of the amino acid cystine within cells, leading to tissue and organ damage. The syndrome is named after Swiss and German physicians who first described the condition in the early 20th century. It primarily affects the kidneys, eyes, and other organs, and symptoms typically appear within the first year of life.

Causes

The syndrome is caused by mutations in the CTNS gene, which encodes the protein cystinosin. Cystinosin is responsible for transporting cystine out of lysosomes (cellular compartments that digest waste). When this transport is impaired due to genetic mutation, cystine accumulates inside lysosomes, forming crystals that damage tissues and organs.

Abderhalden–Kaufmann–Lignac syndrome is inherited in an autosomal recessive pattern. This means a child must inherit two defective copies of the CTNS gene (one from each parent) to develop the condition.

Symptoms

Symptoms of the syndrome typically begin in infancy and progress without treatment. Common signs and symptoms include:

• Renal Fanconi syndrome: A kidney disorder causing loss of essential substances (glucose, phosphate, amino acids, bicarbonate) in urine

• Failure to thrive: Poor weight gain and growth in infancy

• Rickets: Softening and weakening of bones due to phosphate loss

• Polyuria and polydipsia: Excessive urination and thirst due to kidney dysfunction

• Photophobia: Sensitivity to light caused by cystine crystal buildup in the eyes

• Vomiting and dehydration episodes

• Progressive kidney failure: Often developing in later childhood or adolescence

• Muscle wasting and hypotonia (low muscle tone)

Diagnosis

Diagnosis is based on clinical presentation, laboratory testing, and genetic confirmation. Steps may include:

• Urinalysis: Showing evidence of renal Fanconi syndrome (e.g., aminoaciduria, glycosuria, phosphaturia)

• Blood tests: Indicating metabolic imbalances such as acidosis and low phosphate levels

• Slit-lamp eye examination: Detects cystine crystals in the cornea

• Leukocyte cystine measurement: Definitive biochemical test for diagnosing cystinosis

• Genetic testing: Identifies mutations in the CTNS gene

Treatment

Although there is no cure, early and ongoing treatment can significantly improve outcomes. Treatment strategies include:

• Cysteamine therapy: The mainstay of treatment, which reduces intracellular cystine levels and slows disease progression

• Supportive renal management: Includes phosphate, bicarbonate, and electrolyte supplementation

• Vitamin D and calcium: For prevention and treatment of rickets

• Hydration and nutritional support: To manage growth and electrolyte losses

• Kidney transplantation: May be required in cases of end-stage renal disease

• Ophthalmologic care: Topical cysteamine drops can reduce corneal cystine crystals

Prognosis

Without treatment, Abderhalden–Kaufmann–Lignac syndrome can lead to severe complications, including renal failure and growth retardation, often within the first decade of life. However, with early diagnosis and proper cysteamine therapy, the progression of organ damage can be significantly delayed. Many patients now live into adulthood, though long-term management and renal monitoring remain essential. Early intervention is key to improving both life expectancy and quality of life.