Congenital adrenal hyperplasia and genetics
Congenital adrenal hyperplasia (CAH) is a genetic disorder that affects hormone production in the adrenal glands, leading to low levels of cortisol and aldosterone. This condition can result in serious health issues, but with appropriate treatment, individuals with CAH can lead healthy lives. CAH is typically inherited in an autosomal recessive pattern, meaning both parents must carry a mutated gene for their child to be affected. The most common cause of CAH is a mutation affecting the 21-hydroxylase enzyme, while other mutations can involve different enzymes and genes located on various chromosomes.
Symptoms of CAH can differ between genders; for example, female infants may present with ambiguous genitalia, while young boys might show early signs of puberty. Diagnosis often involves blood tests to measure hormone levels, and genetic testing may be recommended for at-risk families. Treatment typically includes lifelong hormone replacement therapy and, in some cases, surgical intervention to correct anatomical anomalies. Understanding CAH and its genetic implications is crucial for affected individuals and their families, particularly regarding treatment options and potential future health considerations.
Congenital adrenal hyperplasia and genetics
ALSO KNOWN AS: Adrenal hyperplasia; CAH
DEFINITION Congenital adrenal hyperplasia (CAH) causes the body to have low levels of certain hormones. The disorder can be life-threatening, but with proper treatment, people with CAH can lead normal, healthy lives.
Parents who suspect their child may have CAH can talk to their child’s doctor about treatment options. Women who are pregnant and suspect their children may be affected by CAH can ask their doctors about testing. Prenatal treatment may also be available; this can correct problems before the child is born.
Risk Factors
CAH is an inherited disorder. Most people who carry the gene for CAH do not have the disorder. Individuals who have someone in their immediate family with CAH can talk to their doctors about genetic testing; this is important if they are expecting or planning to have a child.
Etiology and Genetics
“CAH” is the term applied to a family of diseases that may result from mutations in any one of several genes on five different chromosomes. In each case, the mutant gene causes a deficiency in one of the enzymes involved in the biosynthesis of cortisol (a metabolic and stress hormone) and aldosterone (a hormone responsible for the body's salt-to-potassium balance). All these mutant genes are inherited in an autosomal recessive fashion, which means that both copies of a particular gene must be deficient in order for the individual to be afflicted.
Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected. If one parent has CAH and the other is a carrier, there is a 50 percent probability that each child will be affected. A simple blood test is available to screen for and identify the most common carrier phenotype.
Approximately 90 percent of cases of CAH result from mutations in the gene that encodes the enzyme 21-hydroxylase, which is found on the short arm of chromosome 6 at position 6p21.3. An additional 5–8 percent of cases are caused by 11-beta-hydroxylase deficiency, resulting from mutations in a gene on the long arm of chromosome 8 at position 8q21–22. The remaining cases result from mutant genes located on chromosomes 1 (at position 1p13), 10 (at position 10q24.3), or 15 (at position 15q23-24).
In all cases, the mutant genes encode enzymes that either partially or completely block the conversion of adrenal precursors into cortisol and aldosterone. As a result, there are markedly increased levels of these precursor hormones, which include progesterone and dehydroepiandrosterone (DHEA). It is the presence of excess DHEA that causes the masculinization of female infants during development.
Symptoms
A parent whose child has any of the symptoms of CAH should not assume it is due to CAH. These symptoms may be caused by other, less serious health conditions or by a reaction to medication. Parents should see their child’s doctor if their child experiences any one of the symptoms.
The most obvious symptom in newborn girls is the unusual appearance of genitalia. The labia majora may be fused, and the clitoris may be enlarged, resembling a penis. Instead of separate urethral and vaginal openings, there may be a single tract called a urogenital sinus.
There are no obvious visual symptoms in newborn boys. Boys as young as two or three years old may begin to show signs of puberty. They may become very muscular, experience penis growth, develop pubic hair, and have a deepening voice.
Both boys and girls may have excessive facial and/or body hair. They may also grow very fast compared to other children their age; most will stop growing sooner than their peers and are often relatively short as adults. Boys and girls may have difficulty fighting respiratory infections and illnesses, have high blood pressure, or develop a condition known as “salt wasting,” which is caused by lack of aldosterone and results in dehydration, low blood pressure, a low sodium level, and a high potassium level in the blood. Other possible symptoms include high blood pressure with low blood potassium, poor feeding and vomiting, a failure to gain weight, short stature, and severe acne.
Screening and Diagnosis
A pregnant woman’s doctor will ask about her pregnancy and medical history. The doctor may perform blood or urine tests to check hormone levels, in particular cortisol and aldosterone, or may perform amniocentesis, in which a sample of the fluid that surrounds the baby in the womb is collected and examined.
If a child has already been born, the doctor will ask about the child’s symptoms and medical history, and a physical exam will be conducted. The doctor may take a small amount of blood and urine to test for hormone levels.
In borderline cases, is done with blood tests. A child may also be referred to a specialist. An endocrinologist focuses on hormones; a pediatric urologist focuses on the urinary system in children.
Treatment and Therapy
Parents should talk with their doctors about the best plans for them and their children. Prenatal treatment with dexamethasone is often given if a fetus suspected of having CAH is female. The drug must be administered before gestational week seven to be effective because the adrenal glands and genitals develop in the first trimester. The drug is usually taken as a pill or liquid. If testing later in the pregnancy--typically at week twelve--indicates the fetus does not have CAH, treatment with the drug is stopped. Some concerns have been raised about dexamethasone's impact on neural development, though further study is needed.
Most children born with CAH need to take hormone replacement all of their lives. With constant monitoring, no side effects are expected. The goal of the treatment is to keep the body’s normal balance of hormones. It is important to know that during stressful situations, the dose of cortisol needs to be increased. Individuals should follow their doctors’ directions.
Salt-wasting illness will often require additional table salt in a patient’s diet. Cortisol can increase the appetite, but this can lead to excess weight gain. Calorie intake should be followed closely.
Surgery is required to correct structural anomalies that affect function such as urogenital sinuses and may be performed to change the appearance of unusually formed genitalia, if desired. Parents should work in consultation with specialists in endocrinology, psychology, and urology to make decisions regarding feminizing surgery and be informed of risks, benefits, and their options with regard to the timing of surgical intervention. Sexual function may be negatively affected by surgery; furthermore, opting for a procedure for a non-life-threatening condition at an early age without the patient being able to give consent presents ethical concerns.
Prevention and Outcomes
CAH is an inherited disorder. There are no preventive measures, except the use of dexamethasone.
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