Diabetes maple in children
Introduction
Introduction to Pediatric Maple Diabetes Maple's diabetes, maplesyrupurinedisease (MSUD), is an autosomal recessive disorder. Due to the congenital defects of branched ketoacid dehydrogenase, the catabolism of branched amino acids is blocked, because a large amount of is discharged from the urine of children. Ketone--methylvaleric acid is named after the sweet smell of maple syrup. basic knowledge Sickness ratio: 0.05%-0.08% Susceptible people: children Mode of infection: non-infectious Complications: hypoglycemia, ataxia
Cause
Pediatric maple diabetes cause
(1) Causes of the disease
The disease belongs to autosomal recessive genetic disease, and the defect of branched ketoacid dehydrogenase causes the catabolism of branched amino acids to be blocked.
(two) pathogenesis
The -branched ketoacid (KIC, KMV, KIV) formed by the branched chain amino acid after amino transfer must be further catalytically decarboxylated by a branched -keto acid dehydrogenase in the mitochondria, which is a complex enzyme system (BCKAD). Complex), consisting of decarboxylase (E1, including E1, E1 two subunits), dihydrolipoyltransacylase (E2) and dihydrolipoyl dehydrogenase (E3) Composition, their coding genes are located in 19q13.1-q13.2, 6p21-p22, 1p2l-31 and 7q3l; wherein E3 is also a component of pyruvate dehydrogenase and -ketoglutarate dehydrogenase in human body, This enzyme system also requires thiamine pyrophosphate as a coenzyme, and mutations in any of the above genes lead to defects in this enzyme complex, resulting in various types of maple glucosuria.
Defects of branched ketoacid dehydroxylase cause the corresponding ketoacids to be oxidatively decarboxylated, retained in the body, and excreted in the urine, producing a special odor. The mitochondrial amino acid metabolism disorder increases the branched chain amino acids in the nervous system of the child; glutamic acid, valley Aminoamide and -aminobutyric acid are significantly decreased; medullary lipids such as cerebrosides, proteolipids and cerebroside sulfate are insufficient. It is believed that the accumulation of branched amino acids and ketoacid derivatives in the body is toxic to the brain. Such as inhibiting myelination, interfering with protein synthesis in the brain, inhibiting neurotransmitter function and enzyme activity, causing serious damage to the developing brain tissue, in addition to typical genetic defects, there are three variants, resulting in children Spongiform changes and myelination disorders occur in the white matter of the brain, most prominent in the cerebral hemisphere, corpus callosum, dentate nucleus and pyramidal tract; children with death due to acute metabolic disorders have cerebral edema.
Prevention
Pediatric maple diabetes prevention
Avoiding close relatives, the enzyme activity can be measured by white blood cells or skin fibroblasts. In typical cases, the 14C-labeled leucine can not be changed to 14CO2, the enzyme activity is normal 0 to 2%, and the intermittent type is 8% to 16%. Between the two, the effective form of B1 is more than 25% of normal, and the enzyme activity of heterozygote is 50% of normal. The enzyme activity can be determined by cultured amniotic cells to make prenatal diagnosis and terminate pregnancy if necessary.
Complication
Pediatric maple diabetes complications Complications, hypoglycemia, ataxia
Most children die from recurrent metabolic disorders or neurological dysfunction within a few months after birth. A few survivors also have mental retardation such as mental retardation, spastic paralysis, and cortical blindness. Some treatments may occur concurrently with spastic paralysis, convulsions and coma, may be associated with hypoglycemia, acidosis, intelligent backwardness, ataxia, movement disorders, developmental delay, behavioral changes.
Symptom
Pediatric maple diabetes symptoms common symptoms anterior sputum full infant feeding difficulty gait instability muscle hypertonia weight loss sleepiness diabetes convulsion ketosis acidosis ataxia
This disease is divided into 5 types
1. Typical maple diabetes
This type is the most common and most serious type, and its branched -ketoacid dehydrogenase activity is lower than 2% of normal children. It gradually becomes drowsiness, restlessness, difficulty in breastfeeding, weight loss, etc. on the 4th to 7th day after birth. Symptoms; muscle tension reduction and increase alternately, common to brain-like spasm, convulsions and coma, the disease progresses rapidly, the children have maple syrup in the urine; some children may be associated with hypoglycemia, ketone, acidosis, Most of the children died of recurrent metabolic disorders or neurological dysfunction within a few months after birth. A few survivors also had mental retardation such as mental retardation, spastic paralysis, and cortical blindness.
2. Light (or intermediate) type
The enzyme activity is about 3% to 30% of normal people, the blood chain branched-chain amino acids and branched-chain ketoacids are only slightly increased; the urine has excessive branching ketoacid excretion, and a few may have acute metabolic disorders such as ketoacidosis. Occurrence; this type and thiamine effective type is not easy to identify, clinically applicable therapeutic trials to assist diagnosis.
3. Intermittent type
The enzyme activity is about 5% to 20% of normal people. The child is asymptomatic, with normal physical and mental development, usually in the late stage of infants or in childhood, and also late in adulthood, mostly due to infection, surgery, and photography. Induced by factors such as high protein diet, drowsiness, ataxia, behavioral changes, gait instability, severe convulsions, coma, and even death, the presence of maple syrup in the urine, and the onset of blood in the child. Urine biochemical tests are normal, and a few have low intelligence.
4. Thiamine effective type
The enzyme activity is about 30% to 40% of normal people. The clinical manifestations are similar to those of the intermediate type. The treatment with thiamine (vitamin B1) can improve the clinical symptoms of the child, and the biochemical changes of blood and urine return to normal. The dosage is generally 100-500 mg. /d, while limiting daily protein intake.
5. Dihydrolipoic acid amide dehydrogenase (E3) deficiency
Rarely, the clinical manifestations are similar to the intermediate type, but due to the defects of the E3 subunit, the function of pyruvate dehydrogenase and -ketoglutarate dehydrogenase is also low in addition to the low activity of the branched -ketoacid dehydrogenase. Impaired, it is accompanied by severe lactic acidosis, usually in the first few months of life, gradually appearing progressive neurological symptoms, such as decreased muscle tone, dyskinesia, developmental delay, etc., a large amount of lactic acid, pyruvic acid, alpha in urine - Ketoglutaric acid, -hydroxyisovalerate and -hydroxyketoglutaric acid, etc.; the concentration of alanine in the blood is also increased due to the large accumulation of pyruvic acid.
Examine
Pediatric maple diabetes check
1. Neonatal screening
Most of the disease is screened by Guthrie bacterial growth inhibition method. When the concentration of leucine in the blood is >4 mg/dl (305 mol/L), the amount of ketoacids in the urine should be further tested.
2. Biochemical testing
Electrolyte and blood gas analysis should be performed on clinically diagnosed children. If there is metabolic acidosis and anion gap widening, blood and urine amino acid and organic acid analysis should be performed. Some children may have hypoglycemia in the acute phase.
3. Analysis of amino acids and organic acids
Quantitative detection of amino acids and organic acids in blood, urine or cerebrospinal fluid of children with GC-MS can confirm the diagnosis:
(1) The levels of branched chain amino acids and branched organic acids in the blood are increased.
(2) In the acute phase, the concentration of -ketoisovalerate in the blood is increased, and the -hydroxyisovalerate in the urine is increased.
(3) L-alloisoleucine, which is unique to this disease, can be detected in the blood.
4. Enzymatic detection
The viability of cultured fibroblasts, lymphoblastic branched-chain ketoacid dehydrogenase complexes can be detected.
5. DNA analysis
For family members of known mutation types, DNA can be amplified by PCR and detected with a labeled oligonucleotide probe.
The level of intelligence examination is reduced, the abnormal brain waveform can be seen by EEG examination, and brain edema caused by acute metabolic disorder can be found by brain CT examination.
Diagnosis
Diagnosis and diagnosis of diabetes in children
diagnosis
When the clinical symptoms suggest the disease, a laboratory test is needed to confirm the diagnosis. The screening test of the branched ketoacid in the urine can be tested by ferric chloride (positive of greenish gray) and dinitrophenylhydrazine (positive of yellow precipitate). Check the increase of branched amino acids in blood and urine, which can be determined by paper chromatography or column chromatography. The keto acid can be determined by thin layer chromatography or gas chromatography. The activity of enzyme can be determined by white blood cells or skin fibroblasts. The 14C-labeled leucine is changed to 14CO2, the enzyme activity is normal 0-2%, the intermittent type is 8%-16%, the light type is between the two, and the B1 effective type is normal 25% or more, heterozygous The enzyme activity is 50% normal, and prenatal diagnosis can be made by measuring the enzyme activity using cultured amniocytes.
Differential diagnosis
Children with neurological symptoms should be distinguished from other central nervous system diseases. The urine and sweat of children have maple syrup and laboratory tests can help identify.
