Glutaric aciduria type 1 (GA1) is a rare organic aciduria. It is caused by deficiency of glutaryl-CoA dehydrogenase; a key enzyme in the metabolism of lysine, hydroxylisine and tryptophan. Patients can suffer selective striatal degeneration that presents as motor delay, dystonia or acute motor regression during infancy. The symptoms are due to the accumulation of toxic metabolites and can be precipitated by periods of acute illness, infectious disease, immunizations and surgery. Management of GA1 relies on preemptive diagnosis followed by protein restriction, sustained carbohydrate intake during illness and promoting renal clearance of organic acids. Because the disease is highly treatable if found before brain damage occur, newborn screening has become a pivotal part in the diagnosis of these patients. If untreated, 90% of patients will go on to develop neurological disease.
The intermediate metabolites (glutaric acid, 3-hydroxiglutaric acid (3-OH-GA), glutarylcarnitine (C5DC) and glutaconic acid) that accumulate as a result of the enzyme deficiency, can be detected by gas chromatography/mass spectrometry (GC/MS) or tandem MS. Two groups of patients have been described based on urinary metabolite excretion of glutaric acid; high and low excretors. Newborn screening usually includes identification of C5DC in a blood acylcarnitine profile followed by quantification in urine of 3-OH-GA, followed my molecular genetics confirmation (GCDH gene); in the case of low excretors the urine testing might be falsely negative.
The prevalence of the disease has been estimated at 1 in 100000 newborns but varies within populations. Some communities like the Amish or the Canadian Oji-Cree natives have a high carrier frequency (as high as 1:10)....
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...erstood source of error in the case of false positive newborn screens is the role of perinatal factors such as mode of delivery and its effects on metabolite values.
We have reasons to believe that perinatal factors could in fact affect newborn screen values. Over a span of there years there were 30 cases of positive newborn screens with elevated C5DC values in infants born at Johns Hopkins. All of them considered false positives. Close analysis of the data showed that there were a disproportionate number of cesarean sections in this group of patients as compared to the general population. We believe that there could be a relationship between the mode of delivery (C-section) and the elevated levels of C5DC in newborn screen, either as a direct consequence of the stress of the procedure, or related to the primary indication to undergo a C-section in the first place.
...its role as a coenzyme for L-methylmalonyl-CoA mutase and methionine synthase (e). Serum vitamin B12 less than 145 pg/mL is considered deficient, and is commonly caused by pernicious anemia and atrophic gastritis (k) (h). B12 is measured with a competitive-binding immunoenzymatic assay that measures concentration based on an inverse relationship to absorbance (i). Methylmalonic acid and homocysteine are associated metabolites that increase in concentration with B12 deficiency and act as disease markers (b). The Schilling test is a less common method that involves administration of oral radiolabeled B12, saturation of B12 binding proteins, and subsequent detection of radiolabeled B12 in urine to assess absorption rate (g). Current laboratory methods are rapid and specific, providing clinicians with accurate information in the diagnosis of vitamin B12 deficiency.
Child is a gift from God. Every parent hopes for a healthy child. Abnormalities in the fetus growth have become common nowadays. These abnormalities may be due to physical, radiation and chemical factors. The most common factor is due to genetic mutation, which causes mental retardation, abnormal body buildup and other conditions, which bring a lot of troubles in the future to the child themselves and their parents. Modern technologies and innovations in the medical field had developed a method known as prenatal screening to detect the abnormality before birth and prevent this future tragedy to happen. It is screening for the detection of fetal diseases, usually by ultrasound examination or by testing the amniotic fluid obtained by amniocentesis (Williams & Wilkins, 2004). It is available to all pregnant women. Others screening techniques may include maternal serum, placental biopsy, and genetic test. There are several advantages and disadvantages of prenatal screening.
The child that I tested will be referred to as K.L. I tested her on April 14th 2016. K.L. is 2 years old, with her exact age being 2 years 9 months and 14 days. I called and asked her mother if she would mind dropping K.L. off with me for a few hours so I could perform the test, and then pick her back up after the test was complete. This test more accurate when the caregiver is not present. K.L. has a step sister and a baby brother on the way. She has always been in the daycare setting, because her grandmother is a provider. K.L. was delivered full term via planned cesarean section due to her mother’s small pelvis. There was no complications during this pregnancy. K.L. weighted 8 lbs. 4 oz. and was 20 ½ inches long at birth, now weighting in at ...
In order to fully understand how certain drugs’ cause birth defects it is important to understand how environmental factors affect a developing fetus. When a baby is in the fetal period of development a placenta surrounds the fetus, providing nourishment and also protecting the fetus from harmful substances. This permeable barrier allows for some substances to enter based on a molecule's size, charge and solubility, it is also important to understand that a normal dose of medication for an adult does not affect a fetus in a similar way. Gideon Koren shares many factors that illustrate how and why a drug would affect a fetus more powerfully “…Second, the fetus’s detoxification and immune systems are still immature, unable to clear drugs and other chemicals from its system as effectively as the body of an adult. And third, the fetus is developing so rapidly that even a small disruption induced by a chemical can have far-reaching effects.” These factors help prescribers understand how medications can affect a
Maple syrup urine disease is a rare autosomal recessive disorder of branched-chain amino acid metabolism leading to life-threatening cerebral edema, a swelling caused by excessive fluid in the brain and dysmyeination, malformed and defective myelin sheath, in affected individuals. Maple syrup urine disease is associated with a worldwide frequency of about 1 in 180,000 infants.
Phenylketonuria, or PKU, is “a genetic disorder in which a defective liver enzyme results in the inability to metabolize phenylalanine, an essential amino acid found in all dietary proteins” (Paul, 2000, para. 1). Phenylalanine (Phe) controls the coloring of skin and hair. PKU, if it goes untreated, can cause seizures, behavioral and physical abnormalities, and hinder intellectual growth. While both scientists and doctors have made great strides in testing and treatment of PKU here in the United States, smaller countries still battle the debilitating disorder. This analysis will discuss the history of testing for PKU, the possibility of reverse intellectual impairments of people with PKU, and steps for mothers either looking to become pregnant or are pregnant and afflicted with maternal PKU.
as 3.5 million people are believed to be carriers which means that they have the
The fetus may measure under expected weight, and with later ultrasounds, physical abnormalities may be seen. The use of an ultrasound is not a full proof method of diagnosis for trisomy 18. During the end of the first trimester, pregnant mothers are given the option of prenatal screening to assess the fetal risk of certain chromosomal abnormalities, including trisomy 18. This testing referred to as combined test, combines results from the mother’s blood and the ultrasound results. If results suggest a higher risk probability, a later more conclusive test will be scheduled. During the 15th to 18th week of pregnancy, an amniocentesis or chorionic villus can be performed to have a detailed analysis of the fetal chromosomal material which will show any abnormalities in their karyotype. There is a slight risk with both procedures of injury of the fetus or possible miscarriage. Newer testing has been developed as “non-invasive prenatal diagnosis,” which involves extracting fetal DNA from the mother’s blood sample. After birth, diagnosis is suspected based on physical attributes of the infant. As with before birth, blood testing for chromosome analysis is used for confirmation testing.
Maple syrup urine disease (MSUD) is a metabolic disorder due to deficiency of branched-chain alpha keto acid dehydrogenase enzyme resulting in accumulation of branched-chain amino acids (BCAAs) (leucine, isoleucine, and valine). Prolonged accumulation of leucine and its metabolites may lead to cerebral edema and its lethal complication like cerebral herniation and severe permanent neuronal damage causing psychomotor developmental delay. Lowering the concentration of these metabolic byproducts can prevent permanent neurological damage and may be life saving, particularly when extreme concentrations are reached. A goal of treatment is to rapid removal of toxic metabolites, correction of metabolic abnormalities and prevents further accumulation
Prenatal tests show the possibility of a child having a genetic disorder, such as Down Syndrome which leads many parents to choose abortion. When it comes to prenatal testing there are many different testing options. Screening tests for example, which are the first tests that are done on the fetus. During the first ten to thirteen weeks of a pregnancy, a woman can get a first trimester screening done. This is an ultrasound and maternal blood test that tests for the genes of Down Syndrome and Trisomy 18. In a first trimester screening, a result of 1/50 means a woman has a 2% chance of having a baby with a chromosome disorder (The Facts on Prenatal Testing). The next testing window is the fifteenth – twentieth week of pregnancy. This is a Quad screening and consists of a maternal blood test the looks for Down Syndrome, Trisomy 1, and neural tube defects in the fetus. In this test there is a 5% false positive rate (The Facts on Prenatal Testing). Lastly, in the screening test options is the anatomy ultrasound, which is done eighteenth-twenty-second weeks into pregnancy. This screening is an ultrasound that assesses for birth defects. Screening tests are non-invasive and therefore leave very few negative impacts on the fetus. The majority of this paper will focus on the more invasive tests, such as diagnostic tests.
→Bartter’s Syndrome, or hypochloremic metabolic alkalosis, is a disorder involving a set of three other closely related disorders. These rare congenital Bartter-like syndromes share many pathophysiological simularities, but differ in the age of onset and the location of genetic problems in the nephron (Guay-Woodford).
second, prenatal testing, is a testing of a fetus at risk for the disease. The
A source of error in the lab can occur when the mother’s cells are mistaken for the baby’s cells (“Prenatal Testing”).
Many diseases get a lot of exposure and people know them well. One, however, gets looked over but it affects, “1% to 3% of people.” Geographic
Chambers, C. D., Polifka, J. E., & Friedman, J. M. (2008). Drug safety in pregnant women and their babies: ignorance not bliss. Clinical Pharmacology & Therapeutics, 83(1), 181-183.