Pediatric Copper Deficiency Syndrome
Introduction
Introduction to Pediatric Copper Deficiency Syndrome Copper deficiency syndrome, also known as kinky hairsyndrome (trichopoliodystrophy), also known as copper deficiency hair syndrome, wire-like hair syndrome, Menkes syndrome, Menkes ky hairy syndrome (Menkeskinkyhairsyndrome), Menkes steel hair syndrome (Menkessteelyhairsyndrome) and so on. This symptom is a nutritional deficiency symptom due to the lack of copper due to various reasons. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: anemia
Cause
Causes of Pediatric Copper Deficiency Syndrome
Insufficient intake (25%):
Mainly found in milk-based feeding, milk contains very little copper (average concentration 135g / L), long-term consumption of milk, and malnutrition, or chronic diarrhea, or lack of copper in parenteral nutrition, long-term malnutrition of milk In children, during the recovery period, or partial eclipse, copper deficiency is easy to occur. When feeding nutrients outside the intestine, copper-free solution can be used to copper deficiency.
Insufficient storage (20%):
Premature birth, low birth weight infants lack copper from the mother, to less copper storage in the body, therefore, milk-fed premature infants are prone to copper deficiency.
Absorption barrier (25%):
(1) Affecting the absorption of copper: Zinc can affect the absorption of copper. It has been reported that children or adults take 150-200 mg of zinc per day, which is a deficiency of copper. It has been reported that copper deficiency can occur after Scholl solution for renal tubular acidosis. Alkali treatment can alter the pH of the stomach and small intestine proximal contents and reduce copper absorption.
(2) Congenital intestinal absorption of copper disorders: This disease is associated with congenital genetic defects, X-linked recessive inheritance, congenital copper enzyme activity decreased, to intestinal absorption of copper barrier.
Increased excretion (20%):
Long-term use of a chelating agent formulation that increases urinary copper excretion can result in a lack of copper in the body.
Pathogenesis
Copper is involved in the synthesis of a variety of important enzymes, resulting in a variety of copper deficiency, directly affecting cell redox, tissue respiration and biochemical metabolism, electron transport, iron absorption and transport, red blood cell maturation release, collagen and elastin synthesis, The formation of cytochrome melanin, endocrine and neurotransmitters causes structural and functional abnormalities in the cerebral cortex, cardiovascular, bone and collagen tissues.
Congenital genetic defects to intestinal absorption of copper disorders and copper deficiency, there are four theories: the process of copper ions through the small intestinal mucosal epithelial plasma membrane surface defects, making copper difficult to enter the blood circulation, reducing or preventing copper absorption It is speculated that the protein binding to copper in the intestinal mucosa is mutated, which hinders the release of copper ions from the mucosa and interferes with the transport of copper; the a chain has a recessive mutation and causes disease; the cadmium metabolism disorder causes the metal-binding protein thiol histidine trimethyl inner salt. The performance changes, the copper is transported to the fibroblasts, and other copper-related tissues and cells are deficient in copper and cause disease.
Some signs of copper deficiency are related to the known metabolic function of copper-containing proteases, such as the decrease in anemia and tyrosinase activity in puberty; the decrease in the activity of venous dilatation and the decrease in connective tissue and elastin. According to the study, the synthesis process of hemoglobin and globulin is normal. According to the chronological order, hypokalemia occurs before anemia, while anemia is caused by too little blood iron in the early stage and later into blood. Excessive iron, because iron absorption by transferrin-bound iron transport is reduced, intestinal mucosa, reticuloendothelial system, and increased iron storage in hepatocytes. This lack of storage iron utilization is secondary to the lack of ceruloplasmin, normal The process of maturation of the young red blood cells is impaired by copper deficiency, and it is characterized by low reticulocyte response. There is no exact explanation for the accumulation of intracellular iron. For the synthesis of normal heme in mitochondria, this iron may be ferrous. The form is isolated and cannot be oxidized or transported into cells. A small number of copper-deficient people have low levels of erythropoietin in plasma and urine, but can increase with copper supplementation. Addition, the pathogenesis of leukopenia and neutropenia remains unclear, bone marrow examination reveals granulocyte stem cells, but neutrophil production is impaired.
The copper-deficient skeletal changes are related to defects in collagen synthesis, which is similar to scurvy, because both lead to abnormal collagen, there are few cross-linking bonds in the absence of copper, and the peptide-based lysine and protein hydroxy in the absence of ascorbate Incomplete.
Prevention
Prevention of copper deficiency syndrome in children
Prenatal diagnosis of prenatal diagnosis of congenital copper metabolism utilization deficient disease, can be used for the determination of copper concentration in skin fibroblasts and amniotic fluid cell culture.
Complication
Pediatric copper deficiency syndrome complications Complications anemia
1. Anemia and hypopigmentation anemia.
2. Neurological deficit, epileptic seizures, vision loss, blindness.
3. Repeated infection due to leukopenia, neutropenia, etc. until the resistance is reduced, easy to recurrent infection.
4. Spontaneous fracture collagen synthesis defects lead to abnormal collagen and spontaneous fracture and periosteal reaction.
Symptom
Symptoms of Pediatric Copper Deficiency Syndrome Common Symptoms Repeated infection of hair abnormalities Hepatosplenomegaly Diarrhea Leukopenia Reduced granulocyte reduction Periosteal reaction Anorexia convulsion
Mainly manifested as leukopenia, neutropenia and hypochromic anemia that is ineffective for iron treatment, followed by skin and hair pigmentation, pale, similar to seborrhea dermatitis-like rash, skin is characteristic of pale dry thick, characteristic The hair is abnormal, the hair is curled, the color is light and brittle, and it is easy to break. Under the microscope, the hair enlarges and the stenosis appear alternately. It is called monilethrix, superficial vein dilatation, anorexia, diarrhea, hepatosplenomegaly and growth. Stagnant, small babies may have apnea, central nervous system degeneration, mental retardation, progressive mental retardation 1 to 2 months after birth, epileptic seizures, but also visual loss, blindness, repeated infection and stubbornness Anemia, etc., most children have low body temperature, even those below 35 °C, congenital intestinal absorption of copper disorders only boys, mainly manifested as poor growth, hair curl, seizures and hypothermia, very low birth weight infants Easy to have copper deficiency, clinical manifestations in addition to anemia, neutropenia, as well as bone changes, spontaneous fractures and periosteal Wait.
Examine
Examination of children with copper deficiency syndrome
1. Serum copper examination directly reflects the normal value of copper, neonatal (0.6 ± 0.3) mol / L [(4 ± 2) g / dl], adult (0.4 ± 0.6) mol / L [(2.5 ± 3.7) Gg/dl], the normal value of indirect reaction of copper, neonatal (3.9 ± 0.3) mol / L [(25 ± 2) g / dl], adult 15.2 ~ 16.2 mol / L (97 ~ 103 g / dl), Its clinical significance is consistent with plasma ceruloplasmin oxidase activity, the normal value of total serum copper, neonatal 6.3 ~ 8.6mol / L (40 ~ 55g / dl), gradually increased after birth, 1 month (13 ± 2.2) ) mol / L [(83 ± 14) g / dl], significantly reduced in 2 months, the average (10 ± 0.8) mol / L [(64 ± 5) g / dl], began to increase after 3 months, 6 After the month, it is close to the adult level, the average adult is 17.1~20.4mol/L (109130g/dl), and the normal value of serum copper in healthy children is 1826.5mol/L (115169g/dl), copper deficiency Serum copper was reduced and serum ceruloplasmin levels were reduced.
2. Iron dynamics study reduces iron absorption and the binding of radioactive iron to red blood cells.
3. Liver biopsy normal adult liver copper concentration was determined to be 16 ~ 31g / g, copper deficiency in children with copper deficiency decreased.
Auxiliary inspection
1. X-ray examination showed that the long bones were thickened and accompanied by fractures; the mature cartilage and cancellous bone fragments were visible in the temporary calcification zone; the cortical bone was loose and covered by the activity belt formed by the crescent around the bone. Wound, accompanied by rapid bone calcification and cartilage repair, periosteal thickening, surrounded by edema, cells and thickened connective tissue, anterior rib bulge or depression, spontaneous rib fracture and periosteal reaction, long bone metaphysis It is cup-shaped and extraverted, and is accompanied by spur formation and metaphyseal fracture.
2. Cerebral angiography shows cerebral artery tortuosity, irregular or occluded vascular lumen.
3. Bone marrow examination showed that the red blood cell system was involved and the megaloblasts were changed, and vacuoles were formed. Electron microscopy revealed that red blood cells in the mature stage of the bone marrow predominate, and the young red blood cells have a small amount of heterochromatin and tight nucleoli, cytoplasm. There are many vacuoles of different sizes, even a large amount of ferritin in the vacuoles; some of the wire pulls have iron deposits, which is considered to be hemosiderin, and the granulocyte line shows a decrease in mature cells, but young and middle Granules and promyelocytes are abundant, and iron is also deposited in megakaryocytes and plasma cells.
4. EEG EEG can be abnormal.
5. The concentration of copper in other skin fibroblasts is significantly increased, which is helpful for the diagnosis of congenital copper metabolism and utilization of defective diseases, and can be used for prenatal diagnosis. Amniotic fluid cell culture has the ability to take 64Cu, so amniotic fluid Culture can also be used for the diagnosis of congenital copper-deficient diseases.
Diagnosis
Diagnosis and diagnosis of copper deficiency syndrome in children
Typical cases are not difficult to diagnose. In cases of leukopenia and neutropenia, accompanied by unexplained anemia and radiological changes in the bone suggesting mineral supply disorders, copper deficiency should be considered, if serum copper and copper blue The protein level is low, and the reticulocyte reaction occurs rapidly after copper supplementation, which can be initially diagnosed. If further diagnosis is needed, a liver biopsy should be performed to determine the liver copper content.
Because the internal environment of copper and the biochemical indicators of copper nutrition are affected by many factors, it is necessary to pay more attention when evaluating biochemical examination or diagnosis. For example, plasma copper and ceruloplasmin levels are greatly affected by age and physiological status. The concentration of ceruloplasmin in plasma or cord blood is very low. The full-term infants gradually increase to adult levels at 4-6 months after birth, until they reach 6 years old, and then fall to adult levels.
In the 12 weeks after birth, the immature children showed a continuous low level of plasma copper, and their cord blood copper levels increased with the increase of gestational age.
Hormones have a greater impact on the internal environment stability of copper. According to animal experiments, pituitary excision will cause an increase in liver copper concentration. For example, supplementation of growth hormone, liver copper concentration returns to normal. Therefore, it is speculated that the role of growth hormone may be Regulated by increasing the protein synthesis necessary for normal excretion pathways, bile production after adrenalectomy is reduced, accompanied by a decrease in copper concentration in the bile, and copper concentration in the bile after administration of cortisone returns to normal, plasma copper in patients with adrenal insufficiency The level rises because liver cells increase the cytokine synthesis and secrete copper to the vascular space to maintain the stability of the intracellular environment. What is the role of thyroid hormones in the homeostasis of copper? It is not clear that in humans, the thyroid gland Patients with hyperthyroidism have elevated plasma copper, while patients with hypothyroidism have lower plasma copper levels. Estrogen can induce re-synthesis of ceruloplasmin. Oral contraceptives or pregnancy can lower plasma copper and ceruloplasmin levels. The result of a decrease in estrogen concentration.
In short, in the diagnosis of this disease, we should pay attention to the differential diagnosis, and strive to identify the cause of the diagnosis.
Infants and young children with the above symptoms and signs, especially the characteristic changes of hair, can make a diagnosis, serum copper and plasma ceruloplasmin content decreased, copper-containing enzyme activity decreased, serum copper absorption decreased, EEG abnormalities, etc. have diagnostic value The concentration of copper in skin fibroblasts is significantly increased, which is helpful for the diagnosis of congenital copper metabolism and utilization of deficient diseases, and can be used for prenatal diagnosis. Amniotic fluid cell culture has the ability to take 64Cu, so amniotic fluid culture is also Can be used for diagnosis.
Differential diagnosis
1. Skeletal changes in scurvy copper deficiency are related to defects in collagen synthesis, which is similar to scurvy, because both cause abnormal collagen and bone lesions.
2. Phenylketonuria This disease should be differentiated from phenylketonuria.
