On December 14, 2020, the first snow fell in my city, and pedestrians on the road were immersed in the joy of snow watching. Unlike people who simply go out to enjoy the snow, I went out to the hospital to get my daughter's genetic test report.
It's a rare disease
On the third day of her daughter's birth, the hospital routinely screened for plantar blood. About half a month later, I received a text message on my mobile phone, suggesting that my daughter's genetic metabolic disease in the plantar blood screening program was abnormal and needed to be reviewed.
On the day I received the text message, I took my daughter to the hospital, and the examination report showed that the daughter's isovaleyl carnitine (C5) value was 1.41 μmol/L, while the normal value was 0.03~0.3 μmol/L. The doctor suggested that we repeat the examination, and the C5 value after the review was 1.35 μmol/L, which decreased but was much higher than the normal value.
The doctor said that a high C5 value may indicate isovalerateemia, suggested that it is best to do a genetic test, and briefly explained the disease to us. Isovalerateemia is an autosomal recessive disorder that is only possible if both parents carry one recessive gene at the same loci. For couples married by non-close relatives, the probability of having a child with an autosomal recessive disease is very low.
My husband and I have no family genetic history, pregnancy and obstetric examination is also normal, the child can eat and sleep after birth without any abnormality, we think that genetic testing is just to buy a reassurance, the child is absolutely impossible to suffer from a rare disease with an incidence of only one in hundreds of thousands.
However, a month later, I was hit hard by a genetic test report, which suggested that the IVD gene c.631A> G and c.865G >A heterozygous variants were detected in my daughter's blood, which were inherited from the mother and father, respectively. The IVD gene is associated with isovalerylic acidemia and is autosomal recessive.
After reading the report, my heart sank, but I still had luck and wanted to hear a negative answer from the doctor's mouth. Who knew that the doctor told me after carefully reading the report that the baby was isopretacymic. This is a rare disease, the symptoms are mainly feeding difficulties, nausea and vomiting, drowsiness coma, the body has a special odor, etc., but the disease can be controlled by drugs and special milk powder.
I couldn't accept the fact that my child was suffering from a rare disease and was standing still, like falling into an ice cellar.
The more you know, the less fear you have
I didn't know how I got out of the clinic, but I felt that the world was vast, there was no trace of warmth in my body, and when I reacted, I found that my hands couldn't stop shaking. The probability of winning a lottery ticket is just that, why should my child bear this? On the taxi home, tears fluttering and falling like broken pearls, I clenched my teeth to prevent myself from crying.
When I got home, I took a quick look at the child and immediately opened the computer to search for information about the disease.
Isovalerylic acidemia is an organic acid metabolism disease caused by the accumulation of isovaleryl-CoA dehydrogenase in leucine catabolism, resulting in the accumulation of isovaleric acid and isovaletanyl carnitine in the body. According to the clinical presentation, isovalery acidemia can be divided into acute neonatal and chronic intermittent types, and there are also asymptomatic patients. Acute neonatals generally develop within 2 weeks of life and manifest as vomiting, drowsiness, sweaty foot odor, and chronic intermittent patients usually present with growth retardation. I looked at the child, she was just 2 months old and everything else was fine except for the occasional milk or two.
As soon as I got home, I began to understand the disease. 丨Pixabay
Because it is a rare disease, there is not much information that can be found on the Internet, the information is mixed, some sick children have no problems at all, some children are slow to grow and even die, my heart is in this information.
At night, my husband and I couldn't swallow, and looking at our lovely daughter, we both held our heads and cried, and it was difficult to accept that the child had this rare disease. In the first thirty years of my life, I went to college, went to graduate school, and after graduation, I entered the unit of my choice, and after being introduced to my husband, I knew and loved each other, and I ushered in the crystallization of our love in full of expectation and joy, and everything was so smooth. But just as I entered the year of establishment, I was on the verge of being crushed. It's too hard to accept, my child is so cute and so small, she is a healthy, normal child.
However, reason tells me that things can only be faced when they come, and that avoiding cannot solve any problems. The more I learned about the disease, the less fear I had, and a lot of information told me that the sooner the disease was treated, the better, and the earlier the disease was treated, the less the impact on the child. If the treatment is standardized, the child can grow up like other normal children, and it will not affect schooling, marriage and childbirth.
Rare diseases, while rare, are not necessarily terminal
I forced myself to be strong, the child didn't know anything, and the only thing she could rely on was me. Soon, I hung up the expert number of Xiangya Hospital, and the professor who received the treatment was amiable. After carefully inquiring about the child's situation, the doctor told us: "Although the child has some genetic problems, the disease of isovalerateemia is treatable and controllable. ”
After that, the doctor gave a detailed treatment plan, allowing the child to take left carnitine orally, once every other day, once in a half bottle to reduce the harmful metabolites in the body; at the same time, with special milk powder without leucine feeding every day; and then regularly review, according to the results of the review, adjust the amount of medication and milk powder.
Now, after a period of time, the child is thriving, and every time the child care check-up, the child's development indicators are no problem. My mentality is gradually calm, life is a long process, my child may just be not very beautiful at the beginning of the appearance, in the future stage of life, who said that she can not dance her own gorgeous chapter?
Doctor reviews
Mo ruo | Resident physician, Department of Pediatrics, Tsinghua Changgeng Hospital, Beijing
It can be seen from the text that Bao Dad and Mom have a certain understanding of many basic knowledge of the disease, and in the face of rare diseases that have never been thought of or even unheard of, they can quickly calm their minds and do their best to take the initiative to understand and adhere to the treatment, which is touching and admirable.
The baby's diagnosed isovalerateemia, a genetic metabolic disorder caused by leucine metabolism disorders, is one of the more common forms of organic acidemia, and has gradually become known since its discovery in the 1960s. Mutations in the IVD gene on chromosome 15 can lead to defects in isovaleyl-CoA dehydrogenase (IVD), causing toxic metabolites to accumulate in the body, causing damage to multi-organ systems. The incidence of isovaleric acidemia in Germany is 1:67,000, Portugal at 1:105,000, and Australia at 1:230,750. The statistical incidence of screening in Shanghai Xinhua Hospital in China is 1:190,000, and the statistics of children's hospital affiliated to Zhejiang University are 1:234,000.
The clinical manifestations of isovaleric acidemia are diverse, and symptomatic children can be divided into acute neonatal and chronic intermittent. The former mostly begins to have non-specific symptoms in the neonatal period, common feeding difficulties, vomiting, drowsiness, can be accompanied by a special "sweaty foot" smell, some children will suddenly convulse, coma, and may even be life-threatening. Metabolic acidosis with elevated anion gap, hyperammonemia, blood glucose abnormalities, and cytopenias are common on examination. With age, the incidence of the above clinical manifestations will gradually decrease, and most of them will gradually become chronic intermittent, that is, acute attacks occur intermittently in stressful states such as infection, or some children will have intermittent attacks in the later childhood period. If not treated in time, neurological, cognitive, and developmental abnormalities may occur in the later stage, and some patients may also have pancreatitis, liver fibrosis, optic nerve atrophy and other diseases.
Newborn screening associated with genetic metabolic diseases is by taking heel blood and sending it to the blood acyl carnitine spectrum. With the popularization of screening, more and more children with the third type of isovaleric acidemia, the "asymptomatic type", who have only abnormal biochemical tests but no clinical symptoms, are being diagnosed and treated early. The baby in this article found the problem early through this method.
The diagnosis of the disease is mainly based on blood tandem mass spectrometry (including acyl carnitine spectrometry) and uric organic acid analysis, and the diagnosis is based on the significant increase in serum isovaleyl carnitine (C5) and urinary isoprenelic glycine. Genetic testing, as an adjunct, can provide prenatal diagnosis assistance for the second and third births.
Similar to many organic acid metabolic diseases, in addition to early medical attention at the onset of acute onset, long-term maintenance therapy during remission is essential, that is, "open flow throttling" of toxic metabolites: first, supplementation with levocarnitine and glycine to promote their transformation and excretion; second, restriction of protein and leucine intake to reduce their production, such as the use of special formula milk powder. At the same time, it is necessary to review regularly and adjust individualized treatment. Early diagnosis and adherence to standardized treatment play an extremely important role in preventing morbidity and improving prognosis. Most patients have improved clinical symptoms, and some can work normally, live, and have children.
This little treasure was born with rare diseases, which is very regrettable and pitiful. But fortunately, she was able to detect and treat her early, and even more fortunate to have the meticulous care of her parents and accompany her all the way. I wish the little ones health, happiness and growth!
Sharing personal experience does not constitute a diagnosis and treatment recommendation, can not replace the doctor's individual judgment of a specific patient, if you need to go to a regular hospital.
Author: Miss Puff
Editors: Sylvie, Li Xiaoqiu