Lesch-Nyhan Syndrome: Difference between revisions
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== <big>Introduction</big> == | == <big>Introduction</big> == | ||
Lesch-Nyhan syndrome (LNS) is a rare, inherited X-linked genetic disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT),an enzyme of purine salvage pathway. The enzyme is responsible for recycling purines by converting guanine and hypoxanthine into guanosine monophosphate and inosine monophosphate, respectively. Lack of the enzyme causes an increase in guanine and hypoxanthine, which eventually gets converted into uric acid,<ref>Fu R, Sutcliffe D, Zhao H, Huang X, Schretlen DJ, Benkovic S, Jinnah HA. Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways. Mol Genet Metab. 2015,114(1):55-61.</ref> Uric acid levels are abnormally high in people with Lesch-Nyhan syndrome and sodium urate crystals may abnormally accumulate in the | Lesch-Nyhan syndrome (LNS) is a rare, inherited X-linked genetic disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT),an enzyme of purine salvage pathway. The enzyme is responsible for recycling purines by converting guanine and hypoxanthine into guanosine monophosphate and inosine monophosphate, respectively. Lack of the enzyme causes an increase in guanine and hypoxanthine, which eventually gets converted into uric acid,<ref>Fu R, Sutcliffe D, Zhao H, Huang X, Schretlen DJ, Benkovic S, Jinnah HA. Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways. Mol Genet Metab. 2015,114(1):55-61.</ref> Uric acid levels are abnormally high in people with Lesch-Nyhan syndrome and sodium urate crystals may abnormally accumulate in the joints and kidneys. LNS is inherited as an X-linked recessive genetic disorder that mostly affects males, with rare female exceptions.<ref>[https://www.ninds.nih.gov/health-information/disorders/lesch-nyhan-syndrome#:~:text=What%20is%20Lesch%2DNyhan%20syndrome,present%20at%20birth%20in%20males. https://www.ninds.nih.gov/health-information/disorders/lesch-nyhan-syndrome#:~:text=What%20is%20Lesch%2DNyhan%20syndrome,present%20at%20birth%20in%20males.]</ref> Lesch-Nyhan syndrome was first described in 1964 by Lesch and Nyhan, when two brothers originally diagnosed with [https://www.physio-pedia.com/Cerebral_Palsy_Aetiology_and_Pathology?utm_source=physiopedia&utm_medium=search&utm_campaign=ongoing_internal cerebral palsy] were later recognized as living with a previously undescribed inherited metabolic disease because of the familial occurrence and unusual clinical features.<ref>Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med. 1964;36:561-570.</ref> | ||
== Causes == | == Causes == | ||
Lesch-Nyhan syndrome is an X-linked recessive disorder resulting from mutation of the HPRT1 gene, located at a q26-27 position on the long arm of the X chromosome. Though only a single gene is associated with this syndrome, over 600 mutations have been identified, each leading to varying levels of severity of clinical presentations making HPRT enzyme deficiency a spectrum rather than a single disease.<ref>Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA., Lesch-Nyhan Disease International Study Group. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2014:1282-303.</ref> Males who receive the defective X chromosome from the carrier mothers manifest the disease. Females are mostly carriers but may develop the disease if the healthy X chromosome undergoes lionization, and the defective X chromosome is expressed phenotypically. | Lesch-Nyhan syndrome is an X-linked recessive disorder resulting from mutation of the HPRT1 gene, located at a q26-27 position on the long arm of the X chromosome. Though only a single gene is associated with this syndrome, over 600 mutations have been identified, each leading to varying levels of severity of clinical presentations making HPRT enzyme deficiency a spectrum rather than a single disease.<ref>Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA., Lesch-Nyhan Disease International Study Group. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2014:1282-303.</ref> Males who receive the defective X chromosome from the carrier mothers manifest the disease. Females are mostly carriers but may develop the disease if the healthy X chromosome undergoes lionization, and the defective X chromosome is expressed phenotypically. | ||
== Diagnosis == | |||
== Epidemiology == | |||
The prevalence of Lesch-Nyhan syndrome that has been estimated is between 1:235,000 and 1:380,000.<ref>Jinnah HA, Ceballos-Picot I, Torres RJ, et al. Attenuated varaints of Lesch-Nyhan disease. Brain 2010;133:671–89</ref>Although it is an X-linked genetic disorder manifesting mostly in males, a few females with Lesch Nyhan syndrome have been reported and studies show that it occurs in relatively equal frequencies in all populations. | |||
== References == | == References == | ||
Revision as of 09:37, 24 June 2023
Introduction[edit | edit source]
Lesch-Nyhan syndrome (LNS) is a rare, inherited X-linked genetic disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT),an enzyme of purine salvage pathway. The enzyme is responsible for recycling purines by converting guanine and hypoxanthine into guanosine monophosphate and inosine monophosphate, respectively. Lack of the enzyme causes an increase in guanine and hypoxanthine, which eventually gets converted into uric acid,[1] Uric acid levels are abnormally high in people with Lesch-Nyhan syndrome and sodium urate crystals may abnormally accumulate in the joints and kidneys. LNS is inherited as an X-linked recessive genetic disorder that mostly affects males, with rare female exceptions.[2] Lesch-Nyhan syndrome was first described in 1964 by Lesch and Nyhan, when two brothers originally diagnosed with cerebral palsy were later recognized as living with a previously undescribed inherited metabolic disease because of the familial occurrence and unusual clinical features.[3]
Causes[edit | edit source]
Lesch-Nyhan syndrome is an X-linked recessive disorder resulting from mutation of the HPRT1 gene, located at a q26-27 position on the long arm of the X chromosome. Though only a single gene is associated with this syndrome, over 600 mutations have been identified, each leading to varying levels of severity of clinical presentations making HPRT enzyme deficiency a spectrum rather than a single disease.[4] Males who receive the defective X chromosome from the carrier mothers manifest the disease. Females are mostly carriers but may develop the disease if the healthy X chromosome undergoes lionization, and the defective X chromosome is expressed phenotypically.
Diagnosis[edit | edit source]
Epidemiology[edit | edit source]
The prevalence of Lesch-Nyhan syndrome that has been estimated is between 1:235,000 and 1:380,000.[5]Although it is an X-linked genetic disorder manifesting mostly in males, a few females with Lesch Nyhan syndrome have been reported and studies show that it occurs in relatively equal frequencies in all populations.
References[edit | edit source]
- ↑ Fu R, Sutcliffe D, Zhao H, Huang X, Schretlen DJ, Benkovic S, Jinnah HA. Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways. Mol Genet Metab. 2015,114(1):55-61.
- ↑ https://www.ninds.nih.gov/health-information/disorders/lesch-nyhan-syndrome#:~:text=What%20is%20Lesch%2DNyhan%20syndrome,present%20at%20birth%20in%20males.
- ↑ Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med. 1964;36:561-570.
- ↑ Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA., Lesch-Nyhan Disease International Study Group. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2014:1282-303.
- ↑ Jinnah HA, Ceballos-Picot I, Torres RJ, et al. Attenuated varaints of Lesch-Nyhan disease. Brain 2010;133:671–89
