Galactosemia is a rare recessive disorder caused by the deficiency of galactose- 1 -phosphate uridylyltransferase, leading to the accumulation of toxic levels of galactitol in the blood. It leads to a \(75 \%\) mortality rate in infants as infants cannot metabolize galactose from breast milk. In many countries, newborns are given a heel prick test to measure the levels of metabolic enzymes. As a genetic counselor, how would you explain to a couple whose baby has tested positive for galactosemia where the disease has come from?

Recessive genetic disorders, such as galactosemia, occur when a child inherits two copies of a faulty gene, one from each parent. Each parent is typically a 'carrier', possessing one copy of the altered gene (recessive) and one normal gene (dominant). Carriers usually do not show any symptoms because the normal gene is enough to compensate for the faulty one. However, when two carriers have a child, there is a possibility that the child will receive both recessive genes, leading to the expression of the disorder.

In galactosemia, specifically, the recessive gene causes a deficiency in galactose-1-phosphate uridylyltransferase, an enzyme crucial for metabolizing galactose properly. Without this enzyme, toxic substances build up in the body, causing serious health issues. Understanding this inheritance pattern is crucial for parents to grasp their risks for future pregnancies and genetic counseling can provide insight on how to manage or mitigate this risk.

A Punnett square is a simple graphical way to display all possible genetic combinations from two parents. It's especially useful to predict the likelihood of an offspring having a certain genotype, particularly in the case of recessive genetic disorders such as galactosemia. Each box within the Punnett square represents a possible genetic outcome for the child, with the letters symbolizing the alleles from each parent. For instance, 'G' might represent a normal allele and 'g' a faulty one.

When two carriers (Gg) have children, the Punnett square shows the probability of each genotype: GG (normal), Gg (carrier), and gg (affected by the disorder). Specifically, the chance is 25% for an affected child (gg), 50% for a carrier (Gg), and 25% for a child without the faulty gene (GG). By using this tool, genetic counselors can help couples understand the genetic risks and consider their reproductive options, including genetic testing, before or during pregnancy.

Galactose-1-phosphate uridylyltransferase deficiency is the genetic error at the heart of galactosemia. This enzyme is responsible for converting galactose, a sugar found in milk (including breast milk), into glucose for the body to use as energy. When this enzyme is deficient or nonfunctional due to a mutated gene, the body cannot properly process galactose. As a result, toxic substances, including galactitol, accumulate in the blood, leading to liver damage, intellectual disability, and even death if not treated. Newborn screening programs aim to detect this deficiency early to manage it through dietary restrictions and other interventions.

The critical aspect of managing this deficiency is strict avoidance of lactose-containing foods, which prevents the harmful buildup of galactose and its metabolites. Families with an affected child may benefit from genetic counseling to understand the disease and receive guidance on how to care for an affected child and prepare for future pregnancies.