Pediatric Lesch-Niehan Syndrome
Introduction
Introduction to Pediatric Leish-Nyhan Syndrome Leish-Nyhan syndrome, also known as Ray-Ne syndrome, self-destructive appearance syndrome. Lesch and Nyhan first reported and described the clinical features of the disease in 1964. The clinical features of this disease are boy onset, mental retardation, and dance. Signs of hand and foot, cerebral palsy, compulsive self-mutilation, aggressive behavior and hyperuricemia, etc. Metabolic abnormalities of purine occur in children due to abnormal uric acid metabolism, including Lesch-Niehan syndrome (Lesch -Nyhansyndrome) is more common. basic knowledge The proportion of illness: 0.03% Susceptible people: children Mode of infection: non-infectious Complications: hematuria, urinary tract infection, gouty arthritis
Cause
The cause of children's Lai Shi-Nihan syndrome
(1) Causes of the disease
Leish-Nyhan syndrome is a congenital metabolic disease with concealed recessive inheritance. Seegmiller confirmed in 1965 that the syndrome is defective by hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT). Abnormal metabolism of sputum, accumulation of uric acid, HGPRT is an important part of the salvage pathway, which converts hypoxanthine and xanthine into nucleotides, hypoxanthine nucleotides (IMP) and guanine nucleotides (GMP), LNS The genetic characteristics are X-linked recessive inheritance, and the mother is a gene carrier, specifically invading boys.
(two) pathogenesis
The basic biochemical abnormality of this disease is the defect of the hypoxanthine guanine phosphoribosyltransferase. The HPRT gene is located in Xq26~q27.2, including 9 exons and 8 introns, totaling 57kb, the pathogenesis of this disease. Gene mutations are point mutations or deletions, and there are many types of mutations. In normal cases, HPRT is present in various tissues of the human body and is highly active in the basal ganglia of the brain. The function of this enzyme is to transfer phosphoribosyl to hypoxanthine and Guanine, which forms inosinic acid (IMP) and guanylic acid (GMP), respectively, IMP and GMP have feedback inhibition on the synthesis of indole, and patients with HPRT deficiency, IMP and GMP synthesis Decreased, the inhibition of sputum synthesis is reduced, strontium synthesis is increased, resulting in a large accumulation of uric acid in the terminal product, high uric acidemia, partial defects of HPRT are characterized by gout, and complete loss is manifested by Lesch-Nyhan syndrome. The exact pathogenesis of the disease is not clear, but the central nervous system dopaminergic neurons are almost completely lost. It is speculated that D1-dopamine antagonists may be related to the nervous system of the disease, especially self-harm. As relevant.
Prevention
Pediatric Leish-Nyhan Syndrome Prevention
The HPRT gene has been cloned, and the HPRT mutant gene can be detected by restriction endonuclease fragment length polymorphism (RFLPs) or specific probes; the enzymatic activity is detected by a large number of hair follicles to detect heterozygotes; and amniotic cells are used. Or placental villi, detect the male fetus of the disease, the detection and prenatal diagnosis of the above heterozygotes are possible, provide a reliable method for the effective prevention of the disease, the confirmed male fetus can do selective abortion.
Complication
Pediatric Leish-Nyhan syndrome complications Complications, hematuria, urinary tract infection, gouty arthritis
Have hematuria, urinary tract infection, urinary stones, exercise development backwards, difficulty walking, can induce sudden angular angulation, convulsive seizures, advanced gouty arthritis, gout nodules, giant cell anemia, etc. Kidney dysfunction and death.
Symptom
Pediatric Leish-Nyhan Syndrome Symptoms Common symptoms Aggressive behavior Nutritional disorders Lower limbs Scissors Gait hyperuricemia Bilateral hand and foot Xu moving polyurinary nodules Hematuria involuntary movement Language developmental delay
The clinical features of this disease are the incidence of boys, mental retardation, hand and foot, self-mutilation, aggressive behavior and hyperuricemia.
1. Central nervous system disorders begin to appear neurological symptoms 3 to 4 months after birth, such as involuntary movements of the hands, feet, face, delayed development or regression, 8 to 1 year old performance of extrapyramidal involvement, muscle tension Abnormal (enhanced, hyperthyroidism or dystonia), initial muscle tension is low, dance, hand and foot movement, dyskinesia can not even sit alone, can not stand, can cause walking difficulties, can induce sudden angular arch reversal position, deep reflection Reinforcement, severe torso, extensor tendon of the neck, angulation of the horns, scissors gait in the lower limbs, some Pap stagnation, sputum sputum positive, some patients with nystagmus, visual-motor regulation disorder, with age Muscle spasms and involuntary movements can be slightly improved and semi-random. The child is excited and uneasily begins to develop refractory self-harming behavior at 1 to 2 years old, biting his fingers, tongue and lips, causing it to break. Disability, shouting because of pain, self-mutilation is a kind of compulsive behavior, some slamming into the head, sometimes actively hurting others, language development is delayed, can also send offensive language when speaking, spontaneous The outbreak of anger, swearing, about 50% of the sick children have seizures, mostly mental retardation, but not as serious as dyskinesias, some children can still understand the language, but no one can walk, a few children with near normal intelligence However, there are serious aggressive behaviors, EEG is mostly normal, CT, MRI is normal or has brain atrophy.
2. Children with hyperuricemia are normal at birth and begin to develop normally, but there may be orange-yellow sand-like uric acid crystals on the diaper, or hematuria, urinary tract infection, urinary stones, etc., children with normal blood uric acid concentration, and Urinary uric acid is high, renal dysfunction is impaired in renal tubular function, polyuria, glomerular involvement can cause renal failure, uric acid nephropathy, if not treated, more than 10 years old due to renal insufficiency and death Infants suffering from kidney disease can easily lead to kidney failure, and this disease is more common before puberty.
3. Gout can also have the clinical symptoms of hyperuricemia, ie, urinary calculi, advanced gouty arthritis, gout nodules, giant cell anemia, etc., mostly occur after hyperuricemia 10 to 20 years, HGPRT completely Missed, gout early, rapid progress, gout in childhood may develop into severe disability, all joints can be affected, can be multiple or single gouty arthritis, the most common foot gout, X-ray can be found There is a change in bone quality.
4. Others often vomit, difficulty swallowing, weight loss, low bone age, often die of nutritional disorders, neutrophil chemotaxis, so some children are prone to bacterial infection.
Examine
Pediatric Leish-Nyhan syndrome examination
Increased serum uric acid, usually 357 ~ 595mol / L (6 ~ 10mg / dl), excessive uric acid excretion in urine, > 25mg / (kg · d), uric acid / creatinine ratio increased, normal <1, sick children Up to 2:1 ~ 4:1, the diagnosis depends on the enzyme activity, HPRT in the red blood cells or skin fibroblasts, the activity is reduced or disappeared, the activity of adenine phosphoribosyltransferase is normal or increased, and the heterozygote is detected. Both out and prenatal diagnosis have been possible. Recently, a large number of hair follicles have been used to detect the enzymatic activity to detect heterozygotes. Prenatal diagnosis can be performed with amniocytes or placental villi, and the male fetus can be detected for selective abortion.
The HPRT gene has been cloned and the HPRT mutant gene can be detected by restriction endonuclease fragment length polymorphism (RFLPs) or specific probes.
1. EEG inspection is mostly normal.
2. CT, MRI examination can be normal or have brain atrophy.
3. EEG examination has abnormal brain waves.
4. Urinary angiography can be seen with stones.
Diagnosis
Diagnosis and identification of children's Lai Shi-Nihan syndrome
The diagnosis can be confirmed based on clinical manifestations and laboratory findings.
1. The red blood cell hemolytic product HGPRT activity is reduced, and the residual activity of HGPRT is less than 1% (0.1% to 1%).
2. Urinary uric acid increased, uric acid / creatinine ratio >1.
3. Increased cerebrospinal fluid and hypoxanthine in the urine.
4. Hyperuricemia, usually > 599 mol / L (10 mg / dl), may be normal in children.
5. Prenatal diagnosis of heterozygotes, amniocentesis, amniotic fluid cell culture before 20 weeks of gestation, determination of amniotic fluid cell HGPRT activity loss, early termination of pregnancy.
When clinically suspected LNS, patients with congenital analgesia should be excluded. In addition, some HGPRT, active gout patients with primary gout, atypical neurological symptoms, and HGPRT, a lytic product of red blood cells and fibroblasts, can reach 30%.
Hyperuricemia occurring in childhood is almost secondary to other diseases, such as type I glycogen metabolism, myeloproliferative diseases, drugs such as salicylate, Down syndrome, etc., should be noted.
