1.A Case of Lesch-Nyhan Syndrome Manifesting Only Chronic Gouty Arthritis without Neurologic Symptom.
Yoomi YEO ; Eun Young CHOI ; Hyae Jin YOON ; Sodam JUNG ; Dam KIM ; Seunghun LEE ; Kyung Bin JOO ; Jae Bum JUN
Journal of Rheumatic Diseases 2014;21(4):192-195
Deficiency of hypoxanthine-guanine phosphoribosyltransferase is a purine nucleotide disorder and is the most common genetic cause of uric acid overproduction. This disease has a wide range of spectrum with regard to neurological features depending on the extent of the enzymatic deficiency. Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, called Lesch-Nyhan syndrome, is presented with hyperuricemia and characteristic neurological manifestation and self-mutilation. Partial hypoxanthine-guanine phosphoribosyltransferase--deficient patients are presented with a various intensities of the aforementioned symptoms, from almost normal neurologic manifestation to a severe form along with hyperuricemia. We report a twenty-year-old man with complete hypoxanthine-guanine phosphoribosyltransferase mutation and Lesch-Nyhan sydrome, who manifested gouty arthritis without neurologic symptom.
Arthritis, Gouty*
;
Humans
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase
;
Lesch-Nyhan Syndrome*
;
Neurologic Manifestations*
;
Uric Acid
2.Genetic analysis of a Chinese pedigree with Lesch-Nyhan syndrome.
Dujuan WANG ; Jingjing ZHAO ; Juan TENG ; Wen LI ; Xiangyu ZHAO ; Lin LI
Chinese Journal of Medical Genetics 2023;40(6):723-726
OBJECTIVE:
To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome.
METHODS:
Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing.
RESULTS:
Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance.
CONCLUSION
The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.
Male
;
Humans
;
Female
;
Lesch-Nyhan Syndrome/genetics*
;
Pedigree
;
East Asian People
;
Heterozygote
;
Introns
;
Mutation
3.Analysis of HPRT1 gene variant and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome but no specimen from affected probands.
Ming TONG ; Qian LI ; Anping SUN ; Canming CHEN ; Suwei HU
Chinese Journal of Medical Genetics 2022;39(11):1243-1246
OBJECTIVE:
To carry out genetic testing and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome (LNS) but no specimen from the affected probands.
METHODS:
All affected individuals in this pedigrees were male and had deceased during childhood, with no biological specimen left. Based on their typical neurological dysfunction and tendency for self-mutilation, the diagnosis of LNS was suspected. Sanger sequencing was carried out to detect potential variant of the HPRT1 gene among female members from the pedigree. Following the identification of the pathogenic variant, prenatal diagnosis was provided for a high-risk fetus.
RESULTS:
The proband's mother and three other females were found to harbor heterozygous c.500_501delGGinsC (p.Arg167fs*23) variant of the HPRT1 gene, which was unreported previously. Prenatal diagnosis showed that the fetus was a male and had inherited the same pathogenic variant.
CONCLUSION
The c.500_501delGGinsC variant of the HPRT1 gene probably underlay the LNS in this pedigree. Above finding has provided a basis for prenatal diagnosis and genetic counseling for this pedigree.
Male
;
Female
;
Humans
;
Pregnancy
;
Lesch-Nyhan Syndrome/genetics*
;
Pedigree
;
Hypoxanthine Phosphoribosyltransferase/genetics*
;
Prenatal Diagnosis
;
China
;
Mutation
4.A Case of Lesch-Nyhan Disease Manifesting Gouty Arthritis without Self-mutilation.
Byung Woon KWON ; Kyung Hee HYUN ; Jin Hyung HAN ; So Mi KIM ; Sang Seok LEE ; Young Kwang CHOO ; Eun Kyoung LEE
Korean Journal of Nephrology 2009;28(1):58-62
Lesch-Nyhan disease is a very rare X-linked recessive disorder characterized by mental retardation, spasticity resembling cerebral palsy, choreoathetosis, self-mutilation and hyperuricemia. Self-mutilative behavior is a hallmark of the disease. The underlying defect is a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). We report on a fourteen-year-old boy, who manifested gouty arthritis and mild renal insufficiency with Lesch-Nyhan disease, lacking self-mutilative behavior in spite of undetectable HPRT activity. Though there were several reports about some cases of Lesch-Nyhan disease in the past Korean literature, the cases were classic forms with definite neurological manifestation. As far as we know, this is the first case of Lesch-Nyhan disease without self-mutilation in Korea.
Arthritis, Gouty
;
Cerebral Palsy
;
Gout
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase
;
Intellectual Disability
;
Korea
;
Lesch-Nyhan Syndrome
;
Muscle Spasticity
;
Neurologic Manifestations
;
Renal Insufficiency
5.A Case of Lesch-Nyhan Syndrome.
Joon Sung KIM ; Jae Seung LEE ; Ha Young NOH ; Byung Ju KIM ; Young Jong WOO ; Jee Min PARK ; Myung Gwan KIM ; Gu Hwan KIM ; Han Wook YOO
Journal of the Korean Pediatric Society 2003;46(5):505-509
Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by hyperuricemia, choreoathetosis, spasticity, mental retardation, and compulsive, self-injurious behavior. This disorder results from a complete deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyl transferase(HPRT). We report here on a case of Lesch-Nyhan syndrome in a 1-year, 7-month-old male who presented with frequent vomiting, failure to thrive, and developmental delay. The diagnostic work-up revealed hyperuricemia, hyperuricosuria, and medullary nephrolithiasis. The HPRT activity in the erythrocytes was undetectable with a biochemical assay. We also identified de novo mutation which was a deletion of the 649th base, adenosine, in HPRT gene(649delA) by analysis of cDNA using RT-PCR technique coupled with direct sequencing.
Adenosine
;
DNA, Complementary
;
Erythrocytes
;
Failure to Thrive
;
Humans
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase
;
Infant
;
Intellectual Disability
;
Lesch-Nyhan Syndrome*
;
Male
;
Muscle Spasticity
;
Nephrolithiasis
;
Self-Injurious Behavior
;
Vomiting
6.Anesthetic Experience of Percutaneous Nephrolithotomy for Renal Calculi in a Patient with Lesch-Nyhan Syndrome: A case report.
In Gu JUN ; Ji Hyun CHIN ; Young Kug KIM ; Young Uk KIM ; Sung Kang CHO ; Gyu Sam HWANG ; Jai Hyun HWANG
Korean Journal of Anesthesiology 2007;53(4):520-523
Lesch-Nyhan syndrome (LNS) is a rare, X-linked recessive inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine-phophoribosyltransferase, leading to excessive purine production and elevation of uric acid. Clinical manifestations include mental retardation, spasticity, choreathetosis, compulsive self-mutilation, renal calculi followed by obstructive nephropathy, and arthritis. Patient with LNS may have increased risk of aspiration pneumonia, acute renal failure and unexpected sudden death. We accomplished successful general anesthesia in a case of LNS requiring percutaneous nephrolithotomy due to renal calculi.
Acute Kidney Injury
;
Anesthesia, General
;
Arthritis
;
Death, Sudden
;
Humans
;
Intellectual Disability
;
Kidney Calculi*
;
Lesch-Nyhan Syndrome*
;
Muscle Spasticity
;
Nephrostomy, Percutaneous*
;
Pneumonia, Aspiration
;
Uric Acid
7.Partial HPRT Deficiency Due to a Missense Mutation in the HPRT Gene.
Ju Hee YANG ; Min Hyuk PARK ; Deok Soo KIM ; Jae Won SHIM ; Jung Yeon SHIM ; Hye Lim JUNG ; Moon Soo PARK ; Han Wook YOO
Journal of the Korean Society of Pediatric Nephrology 2003;7(1):86-90
An 8-month-old male infant presented with persistent, gross, orange-colored crystals in his urine. His physical and neurological development was normal. Laboratory study showed hyperuricemia, hyperuricosuria and urate crystaluria. He was determined to have partial hypoxanthine-guanine phosphoribosyl transferase(HPRT) deficiency. The molecular genetic analysis revealed a missense mutation in the patient's HPRT gene. By sequencing the patient's cDNA, we identified an A-to-G transition at nucleotide 239, resulting in the replacement of Aspartate with Glycine at amino acid 80 in the HPRT. To our knowledge, this mutation has not previously been reported. Our patient is now being placed on allopurinol therapy, and has had no problem since. Partial HPRT deficiency has been known to cause recurrent acute renal failure without the phenotypic features of Lesch-Nyhan syndrome. Therefore, we think that early diagnosis and treatment are very crucial in preventing acute renal failure.
Acute Kidney Injury
;
Allopurinol
;
Aspartic Acid
;
DNA, Complementary
;
Early Diagnosis
;
Glycine
;
Humans
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase*
;
Infant
;
Lesch-Nyhan Syndrome
;
Male
;
Molecular Biology
;
Mutation, Missense*
;
Uric Acid
8.Three Cases of Lesch-Nyhan Syndrome: Cases report.
Yong Beom SHIN ; Ji Eui HAN ; Kyung Min KIM ; Song Hyun YANG ; Dae Seong IM
Journal of the Korean Academy of Rehabilitation Medicine 2005;29(6):673-677
Lesch-Nyhan syndrome is a rare X-linked recessive metabolic disorder characterized by developmental delay, hyperuricemia, choreoathetosis, spasticity, mental retardation, and compulsive self-injurious behavior. This disorder results from a complete deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This syndrome is often misdiagnosed to cerebral palsy and clinical manifestations are usually related to the degree of enzyme deficiency. Complete HGPRT deficiency presents with severe specific neurologic manifestation and nephrolithiasis leading to fatal kidney damage. This report highlighted the importance of clinical awareness leading to early diagnosis and therapy for prevention of the self mutilation and renal failure, even if we couldn't inhibit the progression of neuro-psychotic symptoms.
Cerebral Palsy
;
Early Diagnosis
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase
;
Intellectual Disability
;
Kidney
;
Lesch-Nyhan Syndrome*
;
Muscle Spasticity
;
Nephrolithiasis
;
Neurologic Manifestations
;
Renal Insufficiency
;
Self Mutilation
;
Self-Injurious Behavior
9.Molecular characterization and Prenatal Molecular Evaluation of three fetuses in four unrelated Korean families with Lesch-Nyhan syndrome.
Journal of Genetic Medicine 1998;2(1):17-22
The Lesch-Nyhan syndrome which is caused by the deficiency of hypoxanthine guanine phosphoribosyltransferase is an X-linked recessive disorder characterized by hyperuricemia, choreoathetosis, mental retardation and compulsive self-injurious behavior. Clinical management of the patients with the Lesch-Nyhan syndrome is frustrating and requires burdensome medical treatment since it cripples the patient and shortens the life span by progression of neurological symptoms, but there are no cures or measures for relieving relentless natural course of the disease yet. Therefore, prenatal diagnosis of the affected fetus is important in genetic counselling for the family at high risk. In this study, four different mutations in the HPRT gene of four probands have been identified in four unrelated families; K215X, Q109X, nt.631 A, and nt.289 GT. Two mutations among them altered restriction enzyme sites; SpeI for Q109X and MaeI for nt.289 GT. Based on their molecular defects, prenatal diagnoses of 3 the fetuses were successfully made between ninth and eleventh week of gestation by polymerase chain reaction(PCR), restriction digestion and DNA sequencing using cDNA obtained from chorionic villus samples (CVS). We predicted the outcome of all fetuses prenatally. Among the three fetuses two were male and one was female according to the identification made by PCR amplification of the sex determining region of the Y chromosome(SRY) gene. Each carried a wild type allele for the corresponding mutant allele. They were also tested postnatally for the mutations to be unaffected.
Alleles
;
Chorionic Villi
;
Digestion
;
DNA, Complementary
;
Female
;
Fetus*
;
Humans
;
Hyperuricemia
;
Hypoxanthine Phosphoribosyltransferase
;
Intellectual Disability
;
Lesch-Nyhan Syndrome*
;
Male
;
Polymerase Chain Reaction
;
Pregnancy
;
Prenatal Diagnosis
;
Self-Injurious Behavior
;
Sequence Analysis, DNA
10.General Anesthesia for Extracorporeal Shockwave Lithotripsyin Child with Lesch-Nyhan Syndrome.
Sang Jin PARK ; Il chi KWON ; Won Ki LEE ; Deok Hee LEE
Yeungnam University Journal of Medicine 2008;25(1):78-83
Lesch-Nyhan syndrome is an inborn error of purine metabolism resulting from hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) deficiency and leading to excess purine production and uric acid over-production. It is a very rare X-linked recessive disorder, characterized by movement disorder, cognitive deficits, and self-injurious behavior. However, because of the high incidence of calculi, patients may present for surgery of urinary tract, and have increased risk of difficult intubation, aspiration pneumonia, renal insufficiency or sudden death. We report the case of a 5-year-old boy with Lesch-Nyhan syndrome who underwent successive extracorporeal shockwave lithotripsy under general anesthesia.
Anesthesia, General
;
Calculi
;
Child
;
Death, Sudden
;
Humans
;
Incidence
;
Intubation
;
Lesch-Nyhan Syndrome
;
Lithotripsy
;
Movement Disorders
;
Pneumonia, Aspiration
;
Preschool Child
;
Purines
;
Renal Insufficiency
;
Self-Injurious Behavior
;
Uric Acid
;
Urinary Tract