Pediatric ophthalmic-brain-renal syndrome
Introduction
Introduction to pediatric eye-brain-kidney syndrome Oculo-cerebro-renalsyndromeorLowe, also known as Lowe syndrome, is a rare sex-linked recessive genetic disease. Clinically, it is characterized by congenital cataract, low intelligence and renal tubular acidosis. Males are more common, and defects at birth are present, but the symptoms often occur in infancy or later. Eye, brain, and kidney lesions can also occur at different ages, leading to difficulty in diagnosis. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: rickets cataracts glaucoma mental retardation pediatric convulsions chronic renal failure umbilical hernia cryptorchidism
Cause
Pediatric eye-brain-kidney syndrome etiology
(1) Causes of the disease
It is now known that this disease is a recessive inheritance of the X chromosome, which is located at Xp24-p26 and encodes a phosphatase located in the Golgi apparatus.
(two) pathogenesis
1. Pathogenesis: The pathogenesis of this disease is not very clear. In recent years, the disease has been found to be OCRL, located on the X chromosome long arm xq25~26, about 58kb long, containing 24 exons, encoding a 105kb Golgi complex. Protein, which has the activity of phosphatidyli-nositol (4,5)bisphospbate 5-phospHatase, which catalyzes:
Inositol 11,4,5-triphosphate (IP3) is converted to inositol 1,4-diphosphate (IP3);
Inositol 21,3,4,5-tetraphosphate (IP4) is converted to inositol 1,3,4-triphosphate;
Inositol 34,5-diphosphate is converted to inositol tetraphosphate. The inositol phospholipid molecule itself is an intracellular signal molecule or a precursor of a signal molecule. IP2 can be hydrolyzed to diacyl glycerol (DG) and IP3. IP3 and DG are important intracellular messengers. IP3 promotes the release of Ca2 into the endoplasmic reticulum, which initiates the intracellular Ca2 signaling system, while DG activates PKC, which causes the signal to transmit down to play an important physiological function. Therefore, the OCRL gene mutation It will affect the levels of IP2 and IP3. IP2 affects the transport of vesicles in the Golgi complex by regulating the ADP ribosylation level, phospholipase D activity and cytoskeletal actin assembly. The abnormal function of this Golgi complex ultimately leads to Defects in the development of the lens, kidney and nervous system, eventually manifested as Lowe syndrome.
2. Pathological changes: renal pathological changes before the age of 5 only have tubular dilatation, containing protein casts and calcium deposition; renal tubular epithelial cells undergo progressive atrophy after 5 years of age, interstitial fibrosis; some glomerular fibrosis or Glass degeneration, thickening of the basement membrane, pathological changes of the brain including brain atrophy, hydrocephalus, ventricular dilatation, etc., ocular cataract can also be seen.
Prevention
Pediatric eye-brain-kidney syndrome prevention
It is known that this disease is a kind of recessive inheritance of X chromosome. A few female carriers can develop cataract. The prevention of inherited diseases is done according to the preventive measures of hereditary diseases. Hereditary diseases are important causes of affecting the health of infants and children. To influence the quality of the birth population, in order to reduce and reverse the incidence of hereditary diseases, prevention should be carried out from pre-pregnancy to prenatal:
1. Premarital medical examination plays an active role in the prevention of hereditary diseases: the size of the effect depends on the examination items and contents, mainly including serological examination (such as hepatitis B virus, treponema pallidum, HIV), reproductive system examination (such as screening the cervix) Inflammation), general physical examination (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
2. Pregnant women should avoid harmful factors as far as possible: including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals, etc., in the process of antenatal care during pregnancy, systematic screening of birth defects is required. Including regular ultrasound examination, serological screening, etc., if necessary, chromosomal examination, if abnormal results occur, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there is sequelae after birth, whether it can be treated, How to prognose, etc., take practical measures for diagnosis and treatment, children with this disease should also actively prevent infection, and actively symptomatic treatment to prevent the occurrence of various complications.
Complication
Pediatric eye-brain-kidney syndrome complications Complications rickets cataract glaucoma mental retardation children convulsions chronic renal failure umbilical hernia cryptorchidism
Nutritional disorders, rickets, cataracts, glaucoma, mental retardation, convulsions, high blood chlorine tubular infection, chronic renal failure, often complicated by various infections, and may be associated with umbilical hernia, cryptorchidism and other abnormalities.
Symptom
Pediatric eye-brain-kidney syndrome symptoms Common symptoms Osteoporosis high sputum arch proteinuria muscle tension reduction reflex disappeared mental retardation saddle nose corneal opacity photophobia renal diabetes
Most of the children are male, symptoms appear in the months after birth or in childhood, and the eyes, brain and kidneys can appear successively.
1. Main performance: eye, brain, kidney performance:
(1) Brain symptoms: severe mental retardation, low muscle tone, weakened or disappeared tendon reflexes, but no paralysis, and some sick children often continue to cry and cry.
(2) Eye symptoms: congenital bilateral cataract, accompanied by congenital glaucoma (bull eye), severe visual impairment, only light or full blind, often with large nystagmus and photophobia.
(3) renal tubular dysfunction: often renal tubular proteinuria, red blood cells, white blood cells, granular casts; a small number of patients with renal diabetes, medium-to-severe multi-group amino acid urine (lysine, tyrosine More), increased urinary phosphorus, low blood phosphorus, renal tubular reabsorption of bicarbonate and acidification of urine dysfunction, high blood chloride renal tubular acidosis, often distal tracheal acidosis, chronic kidney disease can occur Incomplete function.
2. Other manifestations: Children may have head deformities, such as long head, forehead protrusion, etc.; in addition, saddle nose, sorghum bow and other deformities can be seen, about 1/4 of the children have cryptorchidism, umbilical hernia, rickets and so on.
3. Staging: According to the natural course, it can be divided into 3 phases:
(1) Infancy: This period is characterized by various eye abnormalities and head deformities. The eye is common with congenital cataract and congenital glaucoma. It can be accompanied by nystagmus, eyeball floating movement, blindness, and often blindness. Seeking a doctor, there may be various head deformities such as long head, high forehead, saddle nose, high sacral bow, etc., with severe mental retardation, low muscle tone, weakened or disappeared tendon reflexes, excessive excitement, shouting and even convulsions. The nervous system manifests that there is often no abnormal renal expression in this period, but obvious signs of rickets may appear.
(2) Childhood: As the disease progresses, one or more Fanconi syndromes appear gradually, so the clinical manifestations are incomplete Fanconi syndrome, which may have renal tubular proteinuria, and all amino acids are especially Proteomic acid and tyrosine are obvious, high phosphorusuria can also cause blood phosphorus to decrease, causing anti-vitamin D rickets or osteoporosis, renal tubular acidosis is also more common, and diabetes is often not obvious, and there is no low Blood potassium and polyuria, even if there is a slight performance, in addition, some patients may have umbilical hernia, cryptorchidism and finger arthritis, abnormal eye, crystal opacity, increased intraocular pressure, pupil dilation, corneal opacity, vision loss.
(3) Adulthood: As the disease progresses further, patients may experience varying degrees of renal dysfunction in adulthood and die from complications such as renal failure and malnutrition, and there are reports that female heterozygotes ( The carrier may have only cataract or kidney changes, but the symptoms are mild and there is no abnormal nervous system.
Examine
Pediatric eye-brain-kidney syndrome examination
1. Urine examination: there are red blood cells, white blood cell granules, renal tubular proteinuria, urine sugar, amino acid urine, increased urinary phosphorus, early appearance of amino aciduria, can occur in the neonatal period, urinary ammonia The highest concentration of acid and tyrosine is elevated, hypercalciuria.
2. Blood examination: blood phosphorus decreased, alkaline phosphatase increased, metabolic acidosis, creatinine increased, glomerular filtration rate decreased, hypercholesterolemia.
3. Renal biopsy: glomerular and tubular basement thickening, foot process fusion, interstitial fibrosis.
4. Head imaging examination: the white matter density around the ventricle is reduced in the head, hydrocephalus, brain penetrating malformation, cerebellar dysplasia, etc. MRI can be seen in two types of changes: (1) T2 phase or enhanced scan: irregular flaky High-density shadows may be gliosis or demyelinating lesions, (2) T1 phase and enhanced scan: low-density changes suggest cystic changes.
5. X-ray examination: The sputum-like specific changes can be found in the long bones.
6. Others: EEG, B-ultrasound, electrocardiogram and other routine examinations should be performed. EEG can detect abnormal waveforms of the skull.
Diagnosis
Diagnosis and diagnosis of pediatric eye-brain-kidney syndrome
According to congenital cataract, glaucoma, intelligence and growth and development disorders, the typical performance of Fanconi syndrome, the diagnosis of Lowe syndrome is not difficult, the diagnosis is often because only the congenital changes of the eye are found, while the brain and kidneys are mild or not. Typically, detailed blood and urine biochemical analysis is needed to help diagnose, and if necessary, dynamic observation of changes in the kidneys and brain, which has a greater effect on the establishment of the diagnosis. Since the disease gene has been identified, nearly 20 mutations have been found. More than 60% of patients can detect mutation-causing genes. Therefore, patients with suspected Lowe's eye-brain-kidney syndrome can be screened for OCRL gene mutations, which can confirm patients and carriers, and can be established before the onset of the disease. diagnosis.
It must be differentiated from multiple developmental malformations caused by other causes, severe growth and development disorders caused by vitamin D deficiency or malnutrition, rickets, amino acid urine and eye abnormalities.
