Question

12. Compare mass spectrometry, which is the analytical technique used in newborn screening, to genetic testing to confirm diagnoses.
13. Do web research to distinguish between galactosemia and the lactose intolerance that affects many adults.

Answer 1

12. Newborn screening (NBS), a biochemical test that enables the identification of many inborn errors of metabolism (IEM) a few days after birth. But considering that NBS requires expert chemists, lab technicians, nutritionists, biologists, and medical specialists for metabolic disorders, it cannot only be considered a useful biochemical test, rather it should be considered a complex and integrated program.

The subsequent development of electrospray tandem mass spectrometry in the 1990s permitted the introduction of this new technology into clinical chemistry laboratories, in particular for newborn screening purposes. MS/MS is a versatile, specific, and sensitive technology that provides technicians with the ability of measuring many biomarkers in a single and fast analytical run. People working in the field of newborn screening understood the possibility of passing from one dried blood spot (DBS) for one test and one disorder to one DBS for one multiplex test for many disorders.

Currently, MS/MS can easily identify and quantify—in a run of fewer than 2 minutes —several metabolites such as acylcarnitines, amino acids, succinylacetone, and more recently, some purines. Nowadays, including pilot projects and regionally governed and structured national NBS programs, many labs all around the world screen for more than 40 or more IEM with a single test.

MS/MS technology can help assist the diagnosing of metabolic disorders during the newborn period that was previously diagnosed only after symptoms had developed. Now, presymptomatic detection allows treatment initiation while the infant is healthy and assists in defining the spectrum of clinical disease related to these disorders. MS/MS technology can be used advantageously to screen for selected amino acid disorders for which other newborn screening methods are used. For example, MS/MS can accurately detect elevated phenylalanine levels in dried blood spots taken from infants as young as age <24 hours. By using the MS/MS-detected phenylalanine/tyrosine ratios, physicians can diagnose PKU earlier and rely on an assay with a reduced false-positive rate.

TMS makes possible the simultaneous measurement of several metabolites and, consequently, the detection of several diseases in one blood spot and in unique analysis.

Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible.

13. Galactosemia and Lactose Intolerance

Galactosaemia is an ‘inborn error of metabolism’, i.e., a genetic mistake which means that the person cannot convert the sugar, galactose into anything else and it starts accumulating in the body, causing various problems. Galactose is produced in the intestine and absorbed when lactose is digested - lactose consists of glucose and galactose joined together and when digested by lactase (the enzyme), is split apart into these two smaller sugars. Galactosaemia is a serious lifelong condition.

Lactose intolerance is lack of the digestive enzyme, lactase, and the inability to split the lactose molecule into glucose and galactose, so it cannot be absorbed. Lactose continues through to the large intestine and is either broken down by bacterial flora or excreted unchanged. Lactose intolerance in adults is a normal human condition for 70% of the world's people. See other questions about lactose intolerance for more details.

Unable to breakdown..	Galactose	Lactose
Type of Disorder	Genetic Disorder	Body slowly loses the ability to produce lactase
Causes of Disorder	Caused by production deficiency of several enzymes	Caused by production deficiency of 1 enzyme, specifical lactase
Carbohydrate to avoid	Galactose should be avoided. The body can digest lactose but cannot metabolize galactose once it enters the bloodstream.	Large amounts of lactose should be avoided, as the body cannot breakdown lactose
Treatment?	No known treatment, except avoiding food containing galactose	Commercial enzymes can be used to digest lactose

Causes of Galactosemia: Galactosemia is a hereditary disease. Both parents must pass it down for their child to get it. For example, if your baby has this condition, it means the genes that produce the enzymes to break down galactose into glucose (a sugar) are missing key parts. Without these parts, the genes can’t tell the enzymes to do their job. This causes galactose to build up in the blood, creating problems, especially for newborns.

Three types of galactosemia are present:

• Classic (type I)
• Galactokinase deficiency (type II)
• Galactose epimerase deficiency (type III)

Type I occurs in about 1 in every 30,000-60,000 people. Type II and type III are less common in the population.

As a parent or potential parent, you and your partner can be genetically screened for galactosemia. If you’re a carrier, it doesn’t mean you have to avoid galactose. But, it means you can pass galactosemia along to your children.

Symptoms of Galactosemia

Newborn with classic galactosemia appear normal at birth. Symptoms start to show up within a few days after the newborn starts feeding breast milk or formula with lactose -- the milk sugar that contains galactose.

Newborn first loses appetite and starts vomiting following to jaundice, a yellowing of the skin and the whites of his eyes. Diarrhea is common, too. The disease leads to severe weight loss and the newborn struggles to grow and thrive.

Without treatment, over time newborn/baby may develop cataracts and could be susceptible to infections followed by liver damage and kidney problems. The brain may not mature as well that can cause developmental disabilities. Some children have issues with their motor skills and muscles. For girls, it can cause their ovaries to stop working. Most with this condition can’t have children.

Causes of lactose intolerance

Lactose, a sugar molecule, which is made up of two smaller sugars, glucose and galactose. To be absorbed from the intestine and into the body, lactose must first be split into glucose and galactose. The glucose and galactose are then absorbed by the cells lining the small intestine. The enzyme that splits lactose into glucose and galactose is called lactase, and it is located on the surface of the cells lining the small intestine.

Lactose intolerance is caused by the reduced or absent activity of lactase that prevents the splitting of lactose (lactase deficiency). Lactase deficiency may occur for one of three reasons, congenital, secondary or developmental.

Symptoms

Common symptoms of lactose intolerance are gastrointestinal and include abdominal pain, diarrhea, and flatulence. Less common symptoms include abdominal bloating, abdominal distention, and nausea. Unfortunately, these symptoms can be caused by several gastrointestinal conditions or diseases, so the presence of these symptoms is not very good at predicting whether a person has lactase deficiency or lactose intolerance.