Abderhalden-Kaufmann-Lignac syndrome: Difference between revisions
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{{SK}} [[Abderhalden-Lignac-Kaufmann disease]]; [[nephropathic cystinosis]] | {{SK}} [[Abderhalden-Lignac-Kaufmann disease]]; [[nephropathic cystinosis]] | ||
== | ==Overview== | ||
'''[[Abderhalden-Kaufmann-Lignac syndrome]]''', also called '''[[Abderhalden-Lignac-Kaufmann disease]]''' or '''[[nephropathic cystinosis]]''', is an [[autosomal recessive]] renal disorder of childhood comprising [[cystinosis]] and renal [[rickets]].It is caused by mutations in the CTNS gene encoding for cystinosin, transporting cystine out of the lysosomes. A defect in the cystinosin leads to accumulation of excessive cystine crystals in the lsysosomes of all body [[cells]] and [[organs]]. The most commonly affected organs are the [[eyes]] and [[kidneys]] but it can also affects the [[thyroid]], [[pancreas]], [[gonads]], [[muscles]] and [[CNS]]. The symptoms are [[renal calculi]], [[osteomalacia]], [[aminoaciduria]], [[glycosuria]], [[polyuria]], [[chronic acidosis]], [[hypophosphatemia with vitamin D-resistant rickets]], and often with hypokalemia, [[photophobia]], blepharospasm, [[hypothyroidism]], [[primary hypogonadism in males]], hypotonia, speech delay, [[motor impairment]], [[cognitive dysfunction]], [[Diabetes]], [[hypopigmentation]], coarsened facial features and impaired sweating. The diagnosis is made with measuring cystine levels in [[polymorphonuclear leukocytes]] or cultured [[fibroblasts]]. Molecular analysis of the cystinosin gene can be done for definitive diagnosis.The mainstay of treatment is cystine-depleting therapy with cysteamine. There are no established measures for the primary or secondary prevention of Abderhalden-Kaufmann-Lignac syndrome. | '''[[Abderhalden-Kaufmann-Lignac syndrome]]''', also called '''[[Abderhalden-Lignac-Kaufmann disease]]''' or '''[[nephropathic cystinosis]]''', is an [[autosomal recessive]] renal disorder of childhood comprising [[cystinosis]] and renal [[rickets]].It is caused by mutations in the CTNS gene encoding for cystinosin, transporting cystine out of the lysosomes. A defect in the cystinosin leads to accumulation of excessive cystine crystals in the lsysosomes of all body [[cells]] and [[organs]]. The most commonly affected organs are the [[eyes]] and [[kidneys]] but it can also affects the [[thyroid]], [[pancreas]], [[gonads]], [[muscles]] and [[CNS]]. The symptoms are [[renal calculi]], [[osteomalacia]], [[aminoaciduria]], [[glycosuria]], [[polyuria]], [[chronic acidosis]], [[hypophosphatemia with vitamin D-resistant rickets]], and often with hypokalemia, [[photophobia]], blepharospasm, [[hypothyroidism]], [[primary hypogonadism in males]], hypotonia, speech delay, [[motor impairment]], [[cognitive dysfunction]], [[Diabetes]], [[hypopigmentation]], coarsened facial features and impaired sweating. The diagnosis is made with measuring cystine levels in [[polymorphonuclear leukocytes]] or cultured [[fibroblasts]]. Molecular analysis of the cystinosin gene can be done for definitive diagnosis.The mainstay of treatment is cystine-depleting therapy with cysteamine. There are no established measures for the primary or secondary prevention of Abderhalden-Kaufmann-Lignac syndrome. | ||
[[Image:Autorecessive.svg|100px|left|thumb|autosomal recessive inheritance pattern]] | [[Image:Autorecessive.svg|100px|left|thumb|autosomal recessive inheritance pattern]] | ||
== | ==Historical Perspective== | ||
Abderhalden-Kaufmann-Lignac syndrome was first described by [[Emil Abderhalden]], Swiss biochemist in 1903 as the [[familial cystine accumulation disease]]. Abderhalden referred to a child initially encountered by [[Eduard Kaufmann]], a German physician. [[George Lignac]], a Dutch pathologist, was the first to give more detailed systematic description of the disease and to associate cystinosis with its major clinical manifestations such as [[rickets]], [[renal disease]] and [[growth retardation]]. The disease is named for [[Emil Abderhalden]], [[Eduard Kaufmann]] and [[George Lignac]].<ref name="urlCystinosis – MEDsphere">{{cite web |url=https://medsphere.wordpress.com/2019/12/27/cystinosis/ |title=Cystinosis – MEDsphere |format= |work= |accessdate=}}</ref> | Abderhalden-Kaufmann-Lignac syndrome was first described by [[Emil Abderhalden]], Swiss biochemist in 1903 as the [[familial cystine accumulation disease]]. Abderhalden referred to a child initially encountered by [[Eduard Kaufmann]], a German physician. [[George Lignac]], a Dutch pathologist, was the first to give more detailed systematic description of the disease and to associate cystinosis with its major clinical manifestations such as [[rickets]], [[renal disease]] and [[growth retardation]]. The disease is named for [[Emil Abderhalden]], [[Eduard Kaufmann]] and [[George Lignac]].<ref name="urlCystinosis – MEDsphere">{{cite web |url=https://medsphere.wordpress.com/2019/12/27/cystinosis/ |title=Cystinosis – MEDsphere |format= |work= |accessdate=}}</ref> | ||
== | ==Classification== | ||
Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types: | Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types: | ||
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*'''Non-nephropathic'''(case report): onset on adulthood. Corneal involvement with renal sparing.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | *'''Non-nephropathic'''(case report): onset on adulthood. Corneal involvement with renal sparing.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | ||
== | ==Pathophysiology== | ||
It is thought that Abderhalden-Kaufmann-Lignac syndrome is the result of CTNS gene mutation which encodes for cystinosin, a [[transporter protein]] which carries cystine from lysosomes to cytosol. A defect in the CTNS gene leads to a high level of cystine accumulation in the [[lysosome]]. It is transmitted in autosomal recessive pattern, where inheritance of one [[defective gene]] from each parents who are carrrier, put at risk of their 25% of children manifest the disease. The exact [[pathophysiology]] of the disease is still not properly understood but there are suggested mechanismsm. | It is thought that Abderhalden-Kaufmann-Lignac syndrome is the result of CTNS gene mutation which encodes for cystinosin, a [[transporter protein]] which carries cystine from lysosomes to cytosol. A defect in the CTNS gene leads to a high level of cystine accumulation in the [[lysosome]]. It is transmitted in autosomal recessive pattern, where inheritance of one [[defective gene]] from each parents who are carrrier, put at risk of their 25% of children manifest the disease. The exact [[pathophysiology]] of the disease is still not properly understood but there are suggested mechanismsm. | ||
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#lysosomal cystine accumulation leads to [[cellular ATP depletion]].<ref name="urlAbderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests">{{cite web |url=https://www.medigoo.com/articles/abderhalden-kaufmann-lignac-syndrome/ |title=Abderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests |format= |work= |accessdate=}}</ref> | #lysosomal cystine accumulation leads to [[cellular ATP depletion]].<ref name="urlAbderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests">{{cite web |url=https://www.medigoo.com/articles/abderhalden-kaufmann-lignac-syndrome/ |title=Abderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests |format= |work= |accessdate=}}</ref> | ||
== | ==Causes== | ||
The cause of Abderhalden-Kaufmann-Lignac syndrome is CTNS gene mutation in the [[lysosomal membrane trafficking protein]] called cystinosin, which causes to cystine accumulation in the lysosome of all body [[cells]] and organs, leads to apoptosis and cellular ATP depletion.It is a rare autosomal recessive [[lysosomal storage diseases]].<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue= | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039 }} </ref> | The cause of Abderhalden-Kaufmann-Lignac syndrome is CTNS gene mutation in the [[lysosomal membrane trafficking protein]] called cystinosin, which causes to cystine accumulation in the lysosome of all body [[cells]] and organs, leads to apoptosis and cellular ATP depletion.It is a rare autosomal recessive [[lysosomal storage diseases]].<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue= | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039 }} </ref> | ||
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Abderhalden-Kaufmann-Lignac syndrome must be differentiated from other diseases that cause renal Fanconi syndrome, photophobia, [[blepharospasm]] , and rickets or osteomalacia, such as [[Lowe syndrome]], [[Dent disease]]; [[Idiopathic fanconi syndrome]] | Abderhalden-Kaufmann-Lignac syndrome must be differentiated from other diseases that cause renal Fanconi syndrome, photophobia, [[blepharospasm]] , and rickets or osteomalacia, such as [[Lowe syndrome]], [[Dent disease]]; [[Idiopathic fanconi syndrome]] | ||
== | ==Epidemiology and Demographics== | ||
*The [[incidence]] of Abderhalden-Kaufmann-Lignac syndrome is approximately 0.5-1 per 100,000 live births worldwide. | *The [[incidence]] of Abderhalden-Kaufmann-Lignac syndrome is approximately 0.5-1 per 100,000 live births worldwide. | ||
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*Abderhalden-Kaufmann-Lignac syndrome is a rare disease that tends to affect infants and adolescent.<ref name="urlCystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical">{{cite web |url=https://accessanesthesiology.mhmedical.com/content.aspx?bookid=2674§ionid=220527016 |title=Cystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical |format= |work= |accessdate=}}</ref> | *Abderhalden-Kaufmann-Lignac syndrome is a rare disease that tends to affect infants and adolescent.<ref name="urlCystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical">{{cite web |url=https://accessanesthesiology.mhmedical.com/content.aspx?bookid=2674§ionid=220527016 |title=Cystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical |format= |work= |accessdate=}}</ref> | ||
== | ==Risk Factors== | ||
There are no established risk factors for Abderhalden-Kaufmann-Lignac syndrome. | There are no established risk factors for Abderhalden-Kaufmann-Lignac syndrome. | ||
== | ==Screening== | ||
There is insufficient evidence to recommend routine screening for Abderhalden-Kaufmann-Lignac syndrome. | There is insufficient evidence to recommend routine screening for Abderhalden-Kaufmann-Lignac syndrome. | ||
== | ==Natural History, Complications, and Prognosis== | ||
If left untreated, Abderhalden-Kaufmann-Lignac syndrome may progress to develop chronic renal failure and [[extrarenal complications]] such as [[dwarfism]], [[rickets]], [[hyphothyroidism]], [[hypogonadism]], [[hypopigmentation]], distal vacuolar myopathy, [[osteoporosis]], diabetes, and blindness. | If left untreated, Abderhalden-Kaufmann-Lignac syndrome may progress to develop chronic renal failure and [[extrarenal complications]] such as [[dwarfism]], [[rickets]], [[hyphothyroidism]], [[hypogonadism]], [[hypopigmentation]], distal vacuolar myopathy, [[osteoporosis]], diabetes, and blindness. | ||
Prognosis of Abderhalden-Kaufmann-Lignac syndrome depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment<ref name="pmid26523297">{{cite journal| author=Ariceta G, Camacho JA, Fernández-Obispo M, Fernández-Polo A, Gamez J, García-Villoria J | display-authors=etal| title=Cystinosis in adult and adolescent patients: Recommendations for the comprehensive care of cystinosis. | journal=Nefrologia | year= 2015 | volume= 35 | issue= 3 | pages= 304-21 | pmid=26523297 | doi=10.1016/j.nefroe.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26523297 }} </ref>, life expectancy can extend past 50 years.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | Prognosis of Abderhalden-Kaufmann-Lignac syndrome depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment<ref name="pmid26523297">{{cite journal| author=Ariceta G, Camacho JA, Fernández-Obispo M, Fernández-Polo A, Gamez J, García-Villoria J | display-authors=etal| title=Cystinosis in adult and adolescent patients: Recommendations for the comprehensive care of cystinosis. | journal=Nefrologia | year= 2015 | volume= 35 | issue= 3 | pages= 304-21 | pmid=26523297 | doi=10.1016/j.nefroe.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26523297 }} </ref>, life expectancy can extend past 50 years.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | ||
== | ==Diagnosis== | ||
The diagnosis of Abderhalden-Kaufmann-Lignac syndrome is made with clinical and laboratory findings. The diagnosis is confirmed by [[molecular analysis]] of the cystinosin [[gene]].<ref name="urlCystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical">{{cite web |url=https://accessanesthesiology.mhmedical.com/content.aspx?bookid=2674§ionid=220527016 |title=Cystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical |format= |work= |accessdate=}}</ref> | The diagnosis of Abderhalden-Kaufmann-Lignac syndrome is made with clinical and laboratory findings. The diagnosis is confirmed by [[molecular analysis]] of the cystinosin [[gene]].<ref name="urlCystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical">{{cite web |url=https://accessanesthesiology.mhmedical.com/content.aspx?bookid=2674§ionid=220527016 |title=Cystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical |format= |work= |accessdate=}}</ref> | ||
=== | ===History and Symptoms=== | ||
The hallmark of Abderhalden-Kaufmann-Lignac syndrome is early [[corneal]] cystine crystal deposition. The most common symptoms of Abderhalden-Kaufmann-Lignac syndrome include renal fanconi syndrome, dwarfism, and rickets. Other presenting symptoms of Abderhalden-Kaufmann-Lignac syndrome include photophobia, blepharospasm, aminoaciduria, glycosuria, [[hypokalemia]], vomiting, feeding difficulties, decreased appetite, [[nephrolithiasis]], [[nephrocalcinosis]], distal muscle wasting and weakness, hypothyroidism, hypogonadism, hypopigmentation, diabetes.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | The hallmark of Abderhalden-Kaufmann-Lignac syndrome is early [[corneal]] cystine crystal deposition. The most common symptoms of Abderhalden-Kaufmann-Lignac syndrome include renal fanconi syndrome, dwarfism, and rickets. Other presenting symptoms of Abderhalden-Kaufmann-Lignac syndrome include photophobia, blepharospasm, aminoaciduria, glycosuria, [[hypokalemia]], vomiting, feeding difficulties, decreased appetite, [[nephrolithiasis]], [[nephrocalcinosis]], distal muscle wasting and weakness, hypothyroidism, hypogonadism, hypopigmentation, diabetes.<ref name="urlCystinosis | Radiology Reference Article | Radiopaedia.org">{{cite web |url=https://radiopaedia.org/articles/cystinosis |title=Cystinosis | Radiology Reference Article | Radiopaedia.org |format= |work= |accessdate=}}</ref> | ||
=== | ===Physical Examination=== | ||
The presence of cystine crystal in the cornea, [[growth failure]], [[short stature]], and [[knock-knees]] (valgus deformity) on physical examination is highly suggestive of Abderhalden-Kaufmann-Lignac syndrome.<ref name="urlWhat is Cystinosis? - Cystinosis Research Foundation">{{cite web |url=https://www.cystinosisresearch.org/what-is-cystinosis/ |title=What is Cystinosis? - Cystinosis Research Foundation |format= |work= |accessdate=}}</ref> | The presence of cystine crystal in the cornea, [[growth failure]], [[short stature]], and [[knock-knees]] (valgus deformity) on physical examination is highly suggestive of Abderhalden-Kaufmann-Lignac syndrome.<ref name="urlWhat is Cystinosis? - Cystinosis Research Foundation">{{cite web |url=https://www.cystinosisresearch.org/what-is-cystinosis/ |title=What is Cystinosis? - Cystinosis Research Foundation |format= |work= |accessdate=}}</ref> | ||
=== | ===Laboratory Findings=== | ||
An elevated Cystine concentrations 5-10 nmol half-cystine/mg cell protein in individuals who are [[homozygous]] for Abderhalden-Kaufmann-Lignac syndrome is other diagnostic finding.Reference range levels are below 0.2 nmol half-cystine/mg cell protein. When a fetus is at risk for Abderhalden-Kaufmann-Lignac syndrome, the cystine level can be measured in [[chorionic villi]] or cultured [[amniotic fluid cells]]. | An elevated Cystine concentrations 5-10 nmol half-cystine/mg cell protein in individuals who are [[homozygous]] for Abderhalden-Kaufmann-Lignac syndrome is other diagnostic finding.Reference range levels are below 0.2 nmol half-cystine/mg cell protein. When a fetus is at risk for Abderhalden-Kaufmann-Lignac syndrome, the cystine level can be measured in [[chorionic villi]] or cultured [[amniotic fluid cells]]. | ||
Laboratory findings consistent with the diagnosis of Abderhalden-Kaufmann-Lignac syndrome include serum [[electrolyte]] abnormalities such as [[hypokalemia]], [[hypophosphatemia]], [[hypocalcemia]], [[low bicarbonate levels]], [[hyponatremia]], [[ABG]] to detect [[metabolic acidosis]], and urine test for [[glycosuria]], [[aminoaciduria]], [[proteinuria]].<ref name="urlAbderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests">{{cite web |url=https://www.medigoo.com/articles/abderhalden-kaufmann-lignac-syndrome/ |title=Abderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests |format= |work= |accessdate=}}</ref> | Laboratory findings consistent with the diagnosis of Abderhalden-Kaufmann-Lignac syndrome include serum [[electrolyte]] abnormalities such as [[hypokalemia]], [[hypophosphatemia]], [[hypocalcemia]], [[low bicarbonate levels]], [[hyponatremia]], [[ABG]] to detect [[metabolic acidosis]], and urine test for [[glycosuria]], [[aminoaciduria]], [[proteinuria]].<ref name="urlAbderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests">{{cite web |url=https://www.medigoo.com/articles/abderhalden-kaufmann-lignac-syndrome/ |title=Abderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests |format= |work= |accessdate=}}</ref> | ||
=== | ===Electrocardiogram=== | ||
There are no ECG findings associated with Abderhalden-Kaufmann-Lignac syndrome. | There are no ECG findings associated with Abderhalden-Kaufmann-Lignac syndrome. | ||
=== | ===X-ray=== | ||
There are no specific x-ray findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an x-ray may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which includes [[osteoporosis]], [[urinary tract calcifications]] and [[rickets]]. | There are no specific x-ray findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an x-ray may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which includes [[osteoporosis]], [[urinary tract calcifications]] and [[rickets]]. | ||
=== | ===Echocardiography or Ultrasound=== | ||
There are no echocardiography findings associated with Abderhalden-Kaufmann-Lignac syndrome. | There are no echocardiography findings associated with Abderhalden-Kaufmann-Lignac syndrome. | ||
There are no specific ultrasound findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an ultrasound may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[nephrolithiasis]], and [[renal medullary nephrocalcinosis]]. | There are no specific ultrasound findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an ultrasound may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[nephrolithiasis]], and [[renal medullary nephrocalcinosis]]. | ||
=== | ===CT scan=== | ||
There are no specific CT scan findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a CT scan may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[nephrolithiasis]], [[papilledema]] and [[renal medullary nephrocalcinosis]]. | There are no specific CT scan findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a CT scan may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[nephrolithiasis]], [[papilledema]] and [[renal medullary nephrocalcinosis]]. | ||
=== | ===MRI=== | ||
There are no specific MRI findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a MRI may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[rickets]], [[papilledema]], and [[osteoporosis]]. | There are no specific MRI findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a MRI may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include [[rickets]], [[papilledema]], and [[osteoporosis]]. | ||
=== | ===Other Imaging Findings=== | ||
There are no other imaging findings associated with Abderhalden-Kaufmann-Lignac syndrome. | There are no other imaging findings associated with Abderhalden-Kaufmann-Lignac syndrome. | ||
=== | ===Other Diagnostic Studies=== | ||
Other diagnostic studies for Abderhalden-Kaufmann-Lignac syndrome include [[slit-lamp]] examination, which demonstrates cystine crystals deposition in the cornea. | Other diagnostic studies for Abderhalden-Kaufmann-Lignac syndrome include [[slit-lamp]] examination, which demonstrates cystine crystals deposition in the cornea. | ||
== | ==Treatment== | ||
=== | ===Medical Therapy=== | ||
Symptomatic treatments; | Symptomatic treatments; | ||
*Rehydration | *Rehydration | ||
**High dosage of [[vitamin D]] | **High dosage of [[vitamin D]] | ||
***Electrolyte Supplements- Sodium citrate to treat [[metabolic acidosis]] | ***Electrolyte Supplements- Sodium citrate to treat [[metabolic acidosis]] | ||
****Electrolyte Replacement- Potassium, bicarbonate and phosphate abnormalities treated with [[oral]] or [[intravenous]] supplements.<ref name="urlAbderhalden-Kaufmann-Lignac Syndrome or Nephropathic Cystinosis | Causes | Symptoms | Treatment">{{cite web |url=https://www.epainassist.com/abdominal-pain/kidney/abderhalden-kaufmann-lignac-syndrome-or-nephropathic-cystinosis |title=Abderhalden-Kaufmann-Lignac Syndrome or Nephropathic Cystinosis | Causes | Symptoms | Treatment |format= |work= |accessdate=}}</ref> | ****Electrolyte Replacement- Potassium, bicarbonate and phosphate abnormalities treated with [[oral]] or [[intravenous]] supplements.<ref name="urlAbderhalden-Kaufmann-Lignac Syndrome or Nephropathic Cystinosis | Causes | Symptoms | Treatment">{{cite web |url=https://www.epainassist.com/abdominal-pain/kidney/abderhalden-kaufmann-lignac-syndrome-or-nephropathic-cystinosis |title=Abderhalden-Kaufmann-Lignac Syndrome or Nephropathic Cystinosis | Causes | Symptoms | Treatment |format= |work= |accessdate=}}</ref> | ||
The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is cysteamine. It is available in two formulations; tablet and eyedrops. cysteamine, facilitates lysosomal cystine clearance and delays progression to [[ESRD]], significantly improves [[growth]], decreases the frequency and severity of [[extrarenal complications]], and is associated with extended life expectancy; however, no curative treatment is yet available.<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue= | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039 }} </ref> | The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is cysteamine. It is available in two formulations; tablet and eyedrops. cysteamine, facilitates lysosomal cystine clearance and delays progression to [[ESRD]], significantly improves [[growth]], decreases the frequency and severity of [[extrarenal complications]], and is associated with extended life expectancy; however, no curative treatment is yet available.<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue= | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039 }} </ref> | ||
=== | ===Surgery=== | ||
The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is medical therapy. Surgery is may be needed for patients with complications of Abderhalden-Kaufmann-Lignac syndrome such as End Stage Renal Disease or nephrolithiasis. | The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is medical therapy. Surgery is may be needed for patients with complications of Abderhalden-Kaufmann-Lignac syndrome such as End Stage Renal Disease or nephrolithiasis. | ||
=== | ===Primary Prevention=== | ||
There are no established measures for the primary prevention of Abderhalden-Kaufmann-Lignac syndrome. | There are no established measures for the primary prevention of Abderhalden-Kaufmann-Lignac syndrome. | ||
=== | ===Secondary Prevention=== | ||
There are no established measures for the secondary prevention of Abderhalden-Kaufmann-Lignac syndrome. | There are no established measures for the secondary prevention of Abderhalden-Kaufmann-Lignac syndrome. | ||
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==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
[[Category:Genetic disorders]] | [[Category:Genetic disorders]] | ||
Revision as of 13:08, 16 August 2021
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdulkerim Yassin, M.B.B.S[2]
Synonyms and keywords: Abderhalden-Lignac-Kaufmann disease; nephropathic cystinosis
Overview
Abderhalden-Kaufmann-Lignac syndrome, also called Abderhalden-Lignac-Kaufmann disease or nephropathic cystinosis, is an autosomal recessive renal disorder of childhood comprising cystinosis and renal rickets.It is caused by mutations in the CTNS gene encoding for cystinosin, transporting cystine out of the lysosomes. A defect in the cystinosin leads to accumulation of excessive cystine crystals in the lsysosomes of all body cells and organs. The most commonly affected organs are the eyes and kidneys but it can also affects the thyroid, pancreas, gonads, muscles and CNS. The symptoms are renal calculi, osteomalacia, aminoaciduria, glycosuria, polyuria, chronic acidosis, hypophosphatemia with vitamin D-resistant rickets, and often with hypokalemia, photophobia, blepharospasm, hypothyroidism, primary hypogonadism in males, hypotonia, speech delay, motor impairment, cognitive dysfunction, Diabetes, hypopigmentation, coarsened facial features and impaired sweating. The diagnosis is made with measuring cystine levels in polymorphonuclear leukocytes or cultured fibroblasts. Molecular analysis of the cystinosin gene can be done for definitive diagnosis.The mainstay of treatment is cystine-depleting therapy with cysteamine. There are no established measures for the primary or secondary prevention of Abderhalden-Kaufmann-Lignac syndrome. File:Autorecessive.svg
Historical Perspective
Abderhalden-Kaufmann-Lignac syndrome was first described by Emil Abderhalden, Swiss biochemist in 1903 as the familial cystine accumulation disease. Abderhalden referred to a child initially encountered by Eduard Kaufmann, a German physician. George Lignac, a Dutch pathologist, was the first to give more detailed systematic description of the disease and to associate cystinosis with its major clinical manifestations such as rickets, renal disease and growth retardation. The disease is named for Emil Abderhalden, Eduard Kaufmann and George Lignac.[1]
Classification
Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types:
- Infantile Nephropathic Cystinosis (95%): onset on early infancy.The most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age .
- Juvenile (5%): onset on adolescent.
- Non-nephropathic(case report): onset on adulthood. Corneal involvement with renal sparing.[2]
Pathophysiology
It is thought that Abderhalden-Kaufmann-Lignac syndrome is the result of CTNS gene mutation which encodes for cystinosin, a transporter protein which carries cystine from lysosomes to cytosol. A defect in the CTNS gene leads to a high level of cystine accumulation in the lysosome. It is transmitted in autosomal recessive pattern, where inheritance of one defective gene from each parents who are carrrier, put at risk of their 25% of children manifest the disease. The exact pathophysiology of the disease is still not properly understood but there are suggested mechanismsm.
- Increased cystine levels in the lysosome links to enhanced apoptosis.
- lysosomal cystine accumulation leads to cellular ATP depletion.[3]
Causes
The cause of Abderhalden-Kaufmann-Lignac syndrome is CTNS gene mutation in the lysosomal membrane trafficking protein called cystinosin, which causes to cystine accumulation in the lysosome of all body cells and organs, leads to apoptosis and cellular ATP depletion.It is a rare autosomal recessive lysosomal storage diseases.[4]
Differentiating Abderhalden-Kaufmann-Lignac syndrome from other Diseases
Abderhalden-Kaufmann-Lignac syndrome must be differentiated from other diseases that cause renal Fanconi syndrome, photophobia, blepharospasm , and rickets or osteomalacia, such as Lowe syndrome, Dent disease; Idiopathic fanconi syndrome
Epidemiology and Demographics
- The incidence of Abderhalden-Kaufmann-Lignac syndrome is approximately 0.5-1 per 100,000 live births worldwide.
- Patients of all age groups may develop Abderhalden-Kaufmann-Lignac syndrome.
- Abderhalden-Kaufmann-Lignac syndrome commonly affects infants.
- End Stage Renal Disease is usually first diagnosed among 10-12 years of age with out proper treatment.
- There is no racial predilection to Abderhalden-Kaufmann-Lignac syndrome.
- Male are more commonly affected by Abderhalden-Kaufmann-Lignac syndrome than female. The male to female ratio is approximately 1.5 to 1.
- Although a wide geographic variability has been reported, The majority of Abderhalden-Kaufmann-Lignac syndrome cases are reported in France and Canada. eg, incidence of 1:26,000 in Brittany, France and 1:62,500 in parts of Quebec, Canada.
- Abderhalden-Kaufmann-Lignac syndrome is a rare disease that tends to affect infants and adolescent.[5]
Risk Factors
There are no established risk factors for Abderhalden-Kaufmann-Lignac syndrome.
Screening
There is insufficient evidence to recommend routine screening for Abderhalden-Kaufmann-Lignac syndrome.
Natural History, Complications, and Prognosis
If left untreated, Abderhalden-Kaufmann-Lignac syndrome may progress to develop chronic renal failure and extrarenal complications such as dwarfism, rickets, hyphothyroidism, hypogonadism, hypopigmentation, distal vacuolar myopathy, osteoporosis, diabetes, and blindness.
Prognosis of Abderhalden-Kaufmann-Lignac syndrome depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment[6], life expectancy can extend past 50 years.[2]
Diagnosis
The diagnosis of Abderhalden-Kaufmann-Lignac syndrome is made with clinical and laboratory findings. The diagnosis is confirmed by molecular analysis of the cystinosin gene.[5]
History and Symptoms
The hallmark of Abderhalden-Kaufmann-Lignac syndrome is early corneal cystine crystal deposition. The most common symptoms of Abderhalden-Kaufmann-Lignac syndrome include renal fanconi syndrome, dwarfism, and rickets. Other presenting symptoms of Abderhalden-Kaufmann-Lignac syndrome include photophobia, blepharospasm, aminoaciduria, glycosuria, hypokalemia, vomiting, feeding difficulties, decreased appetite, nephrolithiasis, nephrocalcinosis, distal muscle wasting and weakness, hypothyroidism, hypogonadism, hypopigmentation, diabetes.[2]
Physical Examination
The presence of cystine crystal in the cornea, growth failure, short stature, and knock-knees (valgus deformity) on physical examination is highly suggestive of Abderhalden-Kaufmann-Lignac syndrome.[7]
Laboratory Findings
An elevated Cystine concentrations 5-10 nmol half-cystine/mg cell protein in individuals who are homozygous for Abderhalden-Kaufmann-Lignac syndrome is other diagnostic finding.Reference range levels are below 0.2 nmol half-cystine/mg cell protein. When a fetus is at risk for Abderhalden-Kaufmann-Lignac syndrome, the cystine level can be measured in chorionic villi or cultured amniotic fluid cells. Laboratory findings consistent with the diagnosis of Abderhalden-Kaufmann-Lignac syndrome include serum electrolyte abnormalities such as hypokalemia, hypophosphatemia, hypocalcemia, low bicarbonate levels, hyponatremia, ABG to detect metabolic acidosis, and urine test for glycosuria, aminoaciduria, proteinuria.[3]
Electrocardiogram
There are no ECG findings associated with Abderhalden-Kaufmann-Lignac syndrome.
X-ray
There are no specific x-ray findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an x-ray may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which includes osteoporosis, urinary tract calcifications and rickets.
Echocardiography or Ultrasound
There are no echocardiography findings associated with Abderhalden-Kaufmann-Lignac syndrome. There are no specific ultrasound findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an ultrasound may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include nephrolithiasis, and renal medullary nephrocalcinosis.
CT scan
There are no specific CT scan findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a CT scan may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include nephrolithiasis, papilledema and renal medullary nephrocalcinosis.
MRI
There are no specific MRI findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a MRI may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include rickets, papilledema, and osteoporosis.
Other Imaging Findings
There are no other imaging findings associated with Abderhalden-Kaufmann-Lignac syndrome.
Other Diagnostic Studies
Other diagnostic studies for Abderhalden-Kaufmann-Lignac syndrome include slit-lamp examination, which demonstrates cystine crystals deposition in the cornea.
Treatment
Medical Therapy
Symptomatic treatments;
- Rehydration
- 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.[8]
- Electrolyte Supplements- Sodium citrate to treat metabolic acidosis
- High dosage of vitamin D
The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is cysteamine. It is available in two formulations; tablet and eyedrops. cysteamine, facilitates lysosomal cystine clearance and delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy; however, no curative treatment is yet available.[4]
Surgery
The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is medical therapy. Surgery is may be needed for patients with complications of Abderhalden-Kaufmann-Lignac syndrome such as End Stage Renal Disease or nephrolithiasis.
Primary Prevention
There are no established measures for the primary prevention of Abderhalden-Kaufmann-Lignac syndrome.
Secondary Prevention
There are no established measures for the secondary prevention of Abderhalden-Kaufmann-Lignac syndrome.
Related Chapters
References
- ↑ "Cystinosis – MEDsphere".
- ↑ 2.0 2.1 2.2 "Cystinosis | Radiology Reference Article | Radiopaedia.org".
- ↑ 3.0 3.1 "Abderhalden-Kaufmann-Lignac syndrome - MediGoo - Medical Tests".
- ↑ 4.0 4.1 Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E (2016). "Cystinosis: a review". Orphanet J Rare Dis. 11: 47. doi:10.1186/s13023-016-0426-y. PMC 4841061. PMID 27102039.
- ↑ 5.0 5.1 "Cystinosis | Syndromes: Rapid Recognition and Perioperative Implications, 2e | AccessAnesthesiology | McGraw Hill Medical".
- ↑ Ariceta G, Camacho JA, Fernández-Obispo M, Fernández-Polo A, Gamez J, García-Villoria J; et al. (2015). "Cystinosis in adult and adolescent patients: Recommendations for the comprehensive care of cystinosis". Nefrologia. 35 (3): 304–21. doi:10.1016/j.nefroe.2015.06.010. PMID 26523297.
- ↑ "What is Cystinosis? - Cystinosis Research Foundation".
- ↑ "Abderhalden-Kaufmann-Lignac Syndrome or Nephropathic Cystinosis | Causes | Symptoms | Treatment".