RESUMO
Background: Lesch-Nyhan disease (LND) is a rare X-linked recessive inborn error of purine metabolism. Late diagnosis of LND may cause significant morbidity. LND cases have never been reported in Indonesia.Case report: A 15-year-old male who had been diagnosed with cerebral palsy was referred to our hospital due to renal failure requiring emergency dialysis. The patient presented with three classic manifestations of LND: increased uric acid levels, neurological disorders, and self-injurious behaviors. LND was suspected because of an abscess-like lump on the left ankle that was confirmed to be a tophus, which had burst and discharged thick masses containing blood, debris, and white crystal materials. The diagnosis of LND was confirmed by the presence of a deletion to exon 1 of the HPRT1 gene. The patient received oral allopurinol daily and treatment for end-stage renal disease (ESRD), which included regular dialysis and subcutaneous administration of erythropoietin. At a 2-month follow-up, he improved clinically with a 71% decrease in uric acid levels after regular dialysis and allopurinol treatment.Conclusion: In developed countries, LND can be diagnosed as early as 3 days after birth. However, diagnosis in the present case was delayed due to the rarity of the disease and the limited number of facilities in Indonesia that offer genetic counseling. Late diagnosis of LND leads to ESRD and irreversible abnormalities. This is the first case of LND presenting with a unique clinical presentation of tophus burst reported in Indonesia.
Assuntos
Paralisia Cerebral/complicações , Falência Renal Crônica/etiologia , Síndrome de Lesch-Nyhan/complicações , Síndrome de Lesch-Nyhan/diagnóstico , Adolescente , Alopurinol/uso terapêutico , Diagnóstico Tardio , Éxons , Supressores da Gota/uso terapêutico , Humanos , Hipoxantina Fosforribosiltransferase/genética , Falência Renal Crônica/terapia , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/genética , Masculino , Radiografia Torácica , Diálise Renal , Escoliose/etiologia , Ácido Úrico/sangueAssuntos
Alopurinol/uso terapêutico , Cálculos Renais/tratamento farmacológico , Síndrome de Lesch-Nyhan/tratamento farmacológico , Pré-Escolar , Humanos , Rim/diagnóstico por imagem , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/etiologia , Síndrome de Lesch-Nyhan/complicações , Masculino , Recidiva , Falha de Tratamento , UltrassonografiaAssuntos
Hidratação , Hipoxantina Fosforribosiltransferase/deficiência , Cálculos Renais/terapia , Síndrome de Lesch-Nyhan/complicações , Xantina/metabolismo , Alopurinol/efeitos adversos , Pré-Escolar , Humanos , Concentração de Íons de Hidrogênio , Hipoxantina Fosforribosiltransferase/genética , Rim/diagnóstico por imagem , Rim/metabolismo , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/etiologia , Cálculos Renais/metabolismo , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/metabolismo , Síndrome de Lesch-Nyhan/urina , Masculino , Mutação , Citrato de Potássio/administração & dosagem , Recidiva , Eliminação Renal , Ultrassonografia , Urina/química , Xantina/química , Xantina/urina , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismoRESUMO
BACKGROUND: Lesch-Nyhan syndrome is a rare inborn error of purine metabolism marked by a complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Inherited as an X-linked recessive genetic disorder that primarily affects males, patients with Lesch-Nyhan syndrome exhibit severe neurological impairments, including choreoathetosis, ballismus, cognitive dysfunction, and self-injurious behavior. Uric acid levels are usually abnormally high, leading to kidney and bladder stones which often necessitate urological intervention. Factor V Leiden is an autosomal dominant disorder of blood clotting associated with hypercoagulability, thrombophilia, and renal disease. CASE PRESENTATION: We present the first reported case of xanthine calculi in a patient with Lesch-Nyhan syndrome and Factor V Leiden who was treated with allopurinol. A renal ultrasound and CT scan demonstrated bilateral staghorn calculi in the kidneys as well as nephrocalcinosis. Two years earlier the patient underwent cystoscopy with bilateral ureteroscopy and laser lithotripsy, and he was stone free afterwards. The patient subsequently underwent bilateral percutaneous nephrolithotomy (PCNL) and was stone free following the procedure. Patients with endogenous overproduction of uric acid who are being treated with allopurinol have a higher chance of developing xanthine stones. CONCLUSIONS: Pediatricians treating these children should be aware of these rare conditions and promptly manage the potential complications that may require medical or surgical intervention.
Assuntos
Alopurinol/efeitos adversos , Antimetabólitos/efeitos adversos , Fator V/genética , Cálculos Renais/etiologia , Síndrome de Lesch-Nyhan/complicações , Mutação Puntual , Xantina Oxidase/antagonistas & inibidores , Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Criança , Humanos , Cálculos Renais/sangue , Cálculos Renais/química , Cálculos Renais/terapia , Síndrome de Lesch-Nyhan/sangue , Síndrome de Lesch-Nyhan/tratamento farmacológico , Masculino , Xantina/metabolismoRESUMO
An 11-year-old boy with Lesch-Nyhan syndrome (LNS) had persistently injured himself by biting his lips and buccal mucosa since infancy. Risperidone was only partially effective in suppressing this behavior. Oral administration of S-adenosylmethionine (SAMe), involving increasing the dose from 400 mg to 1 g, resulted in the amelioration of self-injurious behavior and anxiety as well as marked improvement in his self-esteem, performance at school, and friendships. No adverse effects were noted. SAMe may have a favorable effect on symptoms of LNS by activating monoaminergic pathways and/or increasing the adenosine pool in the salvage pathway of guanosine monophosphate synthesis. Defects in these pathways have been essentially implicated in the neurological pathophysiology of LNS.
Assuntos
Síndrome de Lesch-Nyhan/terapia , S-Adenosilmetionina/uso terapêutico , Comportamento Autodestrutivo/tratamento farmacológico , Criança , Humanos , Hipoxantina Fosforribosiltransferase/genética , Síndrome de Lesch-Nyhan/complicações , Masculino , Qualidade de Vida , Comportamento Autodestrutivo/etiologiaRESUMO
CASE REPORT: We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay. CONCLUSION: Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype.
Assuntos
Injúria Renal Aguda/etiologia , Hiperuricemia/etiologia , Síndrome de Lesch-Nyhan/complicações , Esclerose Tuberosa/complicações , Injúria Renal Aguda/terapia , Alopurinol/uso terapêutico , Deficiências do Desenvolvimento/etiologia , Distonia/etiologia , Éxons , Hidratação , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/tratamento farmacológico , Hipoxantina Fosforribosiltransferase/genética , Lactente , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/genética , Masculino , Fenótipo , Convulsões/etiologia , Urato Oxidase/uso terapêuticoRESUMO
As metabolism is controlled by the input of genes and the environment, metabolic disorders result from some disturbance in the interaction between genes and environmental factors. Many metabolic disorders consist in congenital enzyme deficiencies, also known as "inborn errors of metabolism," that may be disabling or cause severe illness and death and are predominantly inherited in an autosomal recessive fashion. The deposit in cells and tissues of storage substances from errors in metabolic processes may produce a wide variety of disorders affecting different organs and functions, with different degrees of severity, and often present around the time of birth or early childhood. Distinctive ocular and skin manifestations accompany many metabolic diseases and may provide clues for their diagnosis and evolution.
Assuntos
Oftalmopatias/etiologia , Erros Inatos do Metabolismo/complicações , Dermatopatias/etiologia , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Amiloidose/complicações , Gota/complicações , Humanos , Síndrome de Lesch-Nyhan/complicações , Proteinose Lipoide de Urbach e Wiethe/complicações , Doenças por Armazenamento dos Lisossomos/complicações , Porfirias/complicaçõesRESUMO
Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior.
Assuntos
Estimulação Encefálica Profunda , Distonia/etiologia , Distonia/terapia , Lateralidade Funcional , Globo Pálido/fisiopatologia , Síndrome de Lesch-Nyhan/complicações , Comportamento Autodestrutivo/etiologia , Comportamento Autodestrutivo/terapia , Acidentes por Quedas , Adolescente , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Distonia/genética , Distonia/fisiopatologia , Eletrodos Implantados , Falha de Equipamento , Humanos , Síndrome de Lesch-Nyhan/genética , Síndrome de Lesch-Nyhan/fisiopatologia , Masculino , Comportamento Autodestrutivo/genética , Comportamento Autodestrutivo/fisiopatologia , Resultado do TratamentoRESUMO
Lesch-Nyhan syndrome is a rare sex-linked disorder of purine metabolism that is caused by a mutation in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene which causes marked hyperuricemia and hyperuricosuria, with signs of gouty arthritis and uric acid stone disease in early childhood. We report a case of renal pelvis calculi which was dissolved within 10 days of urine alkalinization and hydration.
Assuntos
Cálculos Renais/etiologia , Cálculos Renais/terapia , Síndrome de Lesch-Nyhan/complicações , Alopurinol/uso terapêutico , Criança , Hidratação , Humanos , Concentração de Íons de Hidrogênio , Hipoxantina Fosforribosiltransferase/genética , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/urina , Pelve Renal , Síndrome de Lesch-Nyhan/genética , Masculino , Mutação , Tomografia Computadorizada por Raios X , Urina/químicaRESUMO
Lesch-Nyhan syndrome (LNS) is an X-linked disorder originating from deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase. It is characterized by neurological manifestations, including the dramatic symptom of compulsive self-mutilation, which results in destruction of oral and perioral tissues. Several drug trials have been administered to improve the severe self-destructive behaviour, with questionable effectiveness. Invasive treatment approaches, such as extraction of teeth and orthognathic surgery, have been suggested with variable success. A conservative treatment with an intraoral appliance serving to prevent oral and peri-oral self-injury is presented in this report. The patient was a 14-year-old boy demonstrating the typical LNS behaviour, including compulsive self-biting, significant loss of lip and tongue tissue, spasticity and involuntary movements. An acrylic maxillary appliance was designed and constructed with an occlusal plate raising the bite. The appliance was retained by two Adams' clasps on the first premolars, along with three ball clasps between the incisors. Fabrication, insertion, and maintenance were uncomplicated and non-stressful to the patient. Periodic recall over 3-year period has confirmed the effective healing of the oral lesions and a high level of tolerance of the appliance.
Assuntos
Mordeduras Humanas/terapia , Síndrome de Lesch-Nyhan/complicações , Lábio/lesões , Comportamento Autodestrutivo/terapia , Língua/lesões , Adolescente , Mordeduras Humanas/etiologia , Desenho de Equipamento , Seguimentos , Humanos , Masculino , Protetores Bucais , Placas Oclusais , Desenho de Aparelho Ortodôntico , Comportamento Autodestrutivo/etiologia , Resultado do TratamentoRESUMO
We report on a rare case of hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficiency that presented in the newborn period with acute renal failure (ARF). The clinical diagnosis was made on the basis of non-oliguric ARF and evidence of crystal nephropathy on renal biopsy. HGPRT deficiency was eventually confirmed by enzymatic and genetic testing, showing a novel point mutation, 293 A>G. Immediate treatment consisted of peritoneal dialysis with, initially, lactate- then bicarbonate-buffered 1.36% glucose solution together with oral administration of allopurinol. Follow-up after more than 4 years continued to show hyper-echogenic kidneys with almost normal renal glomerular function. There continues to be no neurobehavioural abnormalities.
Assuntos
Injúria Renal Aguda/genética , Hipoxantina Fosforribosiltransferase/genética , Síndrome de Lesch-Nyhan/genética , Mutação Puntual , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Alopurinol/uso terapêutico , Terapia Combinada , Seguimentos , Supressores da Gota/uso terapêutico , Soluções para Hemodiálise , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Hipoxantina Fosforribosiltransferase/metabolismo , Recém-Nascido , Rim/diagnóstico por imagem , Síndrome de Lesch-Nyhan/complicações , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/terapia , Masculino , Diálise Peritoneal , Resultado do Tratamento , UltrassonografiaRESUMO
Lesch-Nyhan syndrome is a very rare X-linked recessive disorder caused by mutation in the gene encoding enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). A complete deficiency of HPRT leads to severe purine overproduction and to uric acid renal lithiasis as a consequence. This may be effectively prevented by administration of allopurinol; however, its overdosage may result in xanthinuria and xanthine urolithiasis. We report on a 9-year-old boy with Lesch-Nyhan syndrome who developed acute renal failure due to bilateral staghorn xanthine urolithiasis resulting from long-term treatment with excessive doses of allopurinol. To the best of our knowledge, the presented case is the first one in the literature.
Assuntos
Injúria Renal Aguda/etiologia , Síndrome de Lesch-Nyhan/complicações , Urolitíase/complicações , Xantinas/urina , Alopurinol/uso terapêutico , Criança , Humanos , Síndrome de Lesch-Nyhan/tratamento farmacológico , Masculino , Urolitíase/tratamento farmacológico , Xantina Oxidase/metabolismoRESUMO
Xanthine calculi are uncommonly encountered stones. When they occur, they typically do so in association with inborn metabolic disorders such as hereditary xanthinuria or Lesch-Nyhan syndrome. They may also occur in association with states of profound hyperuricemia such as myeloproliferative disease after treatment with allopurinol. If the underlying disorder is not addressed, a high risk of stone recurrence exists. Therefore, to raise clinical awareness, we reviewed and report our experience in the treatment of patients with these stones, discussing the underlying pathophysiology and approach to treatment.
Assuntos
Cálculos Renais/etiologia , Cálculos Renais/terapia , Xantina/urina , Adolescente , Alopurinol/efeitos adversos , Criança , Inibidores Enzimáticos/efeitos adversos , Feminino , Hidratação , Humanos , Concentração de Íons de Hidrogênio , Cálculos Renais/química , Síndrome de Lesch-Nyhan/complicações , Litotripsia a Laser , Masculino , Nefrostomia Percutânea , Citrato de Potássio/uso terapêutico , Fármacos Renais/uso terapêutico , Urina/químicaRESUMO
Lesch-Nyhan syndrome is a familial disorder of uric acid metabolism and dysfunction of the central nervous system. We present a patient with the syndrome, who had a defect of the left calcaneal tissue with osteomyelitis caused by repeated self-mutilation. The defect was reconstructed with a sural flap.
Assuntos
Calcâneo/cirurgia , Úlcera do Pé/cirurgia , Síndrome de Lesch-Nyhan/complicações , Retalhos Cirúrgicos , Criança , Úlcera do Pé/etiologia , Humanos , MasculinoRESUMO
Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.
Assuntos
Hiperuricemia/genética , Hipoxantina Fosforribosiltransferase/genética , Síndrome de Lesch-Nyhan/genética , Alopurinol/uso terapêutico , Pré-Escolar , Inibidores Enzimáticos/uso terapêutico , Seguimentos , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Hipoxantina Fosforribosiltransferase/deficiência , Síndrome de Lesch-Nyhan/complicações , Masculino , Mutação Puntual , Resultado do Tratamento , Ácido Úrico/metabolismo , Cálculos Urinários/etiologia , Cálculos Urinários/genéticaRESUMO
A 19-year-old man with Lesch-Nyhan syndrome (LNS), had dyspnea and an inspiratory wheeze, and underwent assisted mechanical ventilation and tracheostomy. Bronchoscopy revealed tracheomalacia of the cresent moon type. He lost his weight, and his general condition gradually worsened. Four months post-tracheostomy, he died of massive hemoptysis from a tracheobrachicephalic artery fistula. Many patients with LNS have renal failure and pneumonitis, whereas occasional cases are complicated by convulsions, recurrent coma, abnormalities of respiration, and sudden death. The etiology of sudden death is not clear. Although tracheomalacia, to our knowledge, has not been described in the literature, it may be a clinical feature of LNS associated with abnormal respiration and sudden death. Tracheobrachiocephalic artery fistula is common in patients with neuromuscular disorders and a chronic tracheostomy tube. Caution is required in LNS patients with opisthotonic extensor spasms of the neck and trunk, chronic bronchitis, and malnutrition.
Assuntos
Artérias , Fístula Artério-Arterial/etiologia , Tronco Braquiocefálico , Broncopatias/etiologia , Doenças das Cartilagens/etiologia , Síndrome de Lesch-Nyhan/complicações , Traqueia/irrigação sanguínea , Doenças da Traqueia/etiologia , Traqueostomia/efeitos adversos , Adulto , Dispneia/etiologia , Dispneia/terapia , Evolução Fatal , Hemoptise/etiologia , Humanos , MasculinoRESUMO
Lesch-Nyhan syndrome (LNS), a rare inborn error of metabolism, is characterized by self-injurious behaviour, which results in partial or total destruction of oral and perioral tissues and/or fingers and hands. Prevention of self-mutilation raises significant difficulties. Treatment modalities include drug therapy, extraction of teeth, oral appliances and orthognathic surgery, all with variable success. A case of a 10-year-old boy with aggressive behaviour and severe lower lip injuries is presented. A palatal plate fabricated to raise the anterior bite proved to have satisfactory results. Although two adjustments were required during the recall visits, the effectiveness of the appliance in assisting healing of soft tissue damage was immediate and still apparent during the 3 years and 8 month follow-up period.
Assuntos
Assistência Odontológica para Doentes Crônicos/métodos , Síndrome de Lesch-Nyhan/complicações , Lábio/lesões , Aparelhos Ortodônticos Removíveis , Comportamento Autodestrutivo/prevenção & controle , Criança , Assistência Odontológica para Crianças , Planejamento de Prótese Dentária , Seguimentos , Humanos , Masculino , Má Oclusão Classe II de Angle/complicações , Comportamento Autodestrutivo/etiologia , CicatrizaçãoRESUMO
Lesch-Nyhan syndrome is an X-linked disorder of purine metabolism. The orthopedic problems and results of treatment of nine Lesch-Nyhan patients are reviewed. Associated orthopedic problems included hip subluxation or dislocation (nine of 18 hips), fractures (three), autoamputation, infections (three), minor scoliosis, and contractures. Lesch-Nyhan patients can safely undergo orthopedic procedures and the results of surgery are satisfactory and similar to those of patients with spastic cerebral palsy. All of the seven operated-on hips maintained good reduction at 6-year mean follow-up. With adequate cast technique, fractures and hip subluxation/dislocation may be treated successfully. The treating orthopedist should be aware of the increased incidence of heterotopic ossification in this population, as well as the potential for serious complications such as hardware failure or femur fracture, if appropriate immobilization is not used.
Assuntos
Articulação do Tornozelo , Fraturas do Fêmur/etiologia , Deformidades Adquiridas do Pé/etiologia , Luxação do Quadril/etiologia , Síndrome de Lesch-Nyhan/complicações , Fraturas do Rádio/etiologia , Escoliose/etiologia , Adolescente , Adulto , Criança , Humanos , Estudos RetrospectivosRESUMO
Esta curiosa enfermedad, descrita en 1964, tiene una baja incidencia (1 en 100.000 a 1 en 380.000 personas-año). No tiene prevalencia geográfica ni étnica. Aunque al nacer el niño parece normal, la sintomatología aparece en los primeros meses de vida. Se produce un retardo del desarrollo psicomotor con una sorprendente compulsión a automutilarse especialmente los labios, lengua y mejillas. Puede también golpearse los dedos, manos o la cabeza con una conducta autoagresiva. Además hay habitualmente movimientos coreoatetósicos y espasticidad. La mayoría logra caminar pero, con el avance de la enfermedad, quedan inválidos. Se retrasa la adquisición del lenguaje y hay disartria permanente
Assuntos
Automutilação/complicações , Doença de Huntington/complicações , Síndrome de Lesch-Nyhan/complicações , Alopurinol/uso terapêutico , Doença de Huntington/diagnóstico , Doença de Huntington/tratamento farmacológico , Doença de Huntington/etiologia , Hipoxantina Fosforribosiltransferase/deficiênciaRESUMO
The authors report a case of xanthine stones in a 12-year-old child with Lesh Nyhan syndrome treated by allopurinol at the dose of 10 mg/kg/24 hours. This type of urinary stone is unusual and its structure was confirmed by spectrophotometric analysis. This type of stone, in the context of Lesh Nyhan syndrome, suggests the presence of allopurinol treatment. Discontinuation of this treatment prevents recurrence of xanthine stones.