Prenatal Diagnosis Heredity Disorders Other Biochemical

Prenatal Diagnosis: Heredity Disorders, Other Biochemical Diseases, And
Disfiguring Birth Defects Essay, Research Paper

Prenatal Diagnosis: Heredity Disorders, Other Biochemical Diseases, and

Disfiguring Birth Defects

There are over 250 recognized sex-linked diseases, affecting every organ

system. Of these, 95% affect males, (Emery, 1968). Despite these many sex-

linked diseases, at present prenatal diagnosis can specifically be made in fewer

than 40 diseases. (Emery, 1968). These sex-linked diseases are individual rare

and some are named after physicians who described them, for example, Hemophilia

A and B, Duchenne muscular dystrophy, fragile-X syndrome, Fabry disease, Hunter

syndrome, Lesch-Nyhan syndrome, and Menkes steely-hair syndrome. The following

discourse considers the reasons for the importance of prenatal diagnosis,

heredity disorders, and disfiguring birth defects.(Nora,1989).

Fabry disease is a biochemical disorder caused by a missing enzyme.

(Mulinsky, 1989). A complex fatty substance accumulates in the body because of

the missing enzyme which would ordinarily break this compound into

pieces.(Nora,1989). This missing enzyme causes kidney and blood-vessel problems

that lead to high blood pressure, kidney failure and strokes.(Mulinsky, 1989).

After many years of symptoms, most patients have died in their thirties and

forties owing to a lack specific treatment.

A biochemical disorder also caused by a missing enzyme is the Lesch-

Nyhan syndrome, an extremely unpleasant disorder characterized not only by

profound mental retardation and features of brain damage (stiff limbs with

peculiar movements), but also self-mutilation, (Jones, 1988). Given good care

and attention however, these patients may live on many years in their profoundly

retarded state. They often require restraining, tying their hands, to prevent

them from mutilating themselves.

Another Affected children with Menkes steely-hair syndrome have hair

that feels similar to steel wool; in addition, they are retarded. The basic

defect in this condition concerns the way the body handles copper.

Only a few of these sex-linked disorders can now be diagnosed in the

fetus, (Stein, 1994). At the present time, the only recourse parents have in

the case of sex-linked diseases that are not prenatally diagnosable is to

determine the sex of the fetus. If a female fetus is found, the parents can be

reassured that their child will not be affected (a critical exception is

fragile-X). However, if it is determined that there is a male fetus present,

there is a fifty percent chance that it is affected, (Milunsky, 1989). Since

there is no way of being certain, the parents must decide simply on the basis of

high risk weather to take a chance or terminate that pregnancy.

There are some unusual sex-linked diseases that are confined to females.

Disorders of this kind (such as incontinentia pigmenti, a skin disorder

associated with brain damage) can be managed by determining weather the fetus is

a female. In this group, virtually all females will be affected, and the

parents could selective elect to have unaffected boys.

Hemophilia A and Duchenne muscular dystrophy are two of the most common

sex-linked diseases that are familiar to most people. But there are so many

other diseases that great care must be taken by both the doctor and the family

in obtaining an accurate family history. Renpenning syndrome, in which there is

mental retardation without any other physical signs, is confined to males. The

only way to suspect sex-linked inheritance is for the physician to carefully

analyze the family lineage. Tests are preformed to detect female carriers of

such diseases. For example, almost all carriers of hemophilia and Duchenne

muscular dystrophy can now be detected. A muscle enzyme, creatine phosphokinase,

which leaks into the blood is also often measured to give a higher probability

of recognizing a carrier. Unfortunately, because of recombination, the

carrier-detection tests for both hemophilia and muscular dystrophy do not

provide answers in 100 percent of cases. A negative result causes uncertainty

and leaves the question of carrier detection basically unanswered. Fortunately,

carrier-detection tests are steadily becoming possible in more of the sex-linked

and other disorders.

Prenatal Studies for Heredity Biochemical Disorders

Many hundreds of different hereditary biochemical disorders of

metabolism are known. About 1 in every 100 children born have one of these

biochemical disorders. (Nora, 1989). Many of these disorders do not cause

mental retardation, or impair the child’s normal development or general health

to any great extent, if at all. Many others, however, cause severe mental

retardation, seizures, stunting of growth, and early death. Close to 150 of

these biochemical disorders can now be diagnosed in the affected fetus early in

pregnancy. (Nora,1989). The first diagnosis of a biochemical disorder in the

fetus while in the womb was made in the late 1960’s; the disorder was Tay-Sachs

disease. (Emery, 1968). Diagnosis such as this are made by obtaining cells from

the amniotic fluid which are placed in small dishes containing a nutrient broth,

and then kept in a special warm, moist incubator. They grow slowly. After a

period of two to three weeks or, occasionally, as long as six weeks, there are

enough cells to work on. Each of the cells having the genetic blueprint will

show the specific biochemical defect ( for example, deficient activity of an

enzyme) thereby enabling a diagnoses to be made. With diagnosis, physicians

can treat the known disorder through the womb.

For a few disorders, such as Rh disease, treatment of the fetus directly

or through the mother has now succeeded. The first prenatal diagnosis of a

biochemical disorder that was treatable in the womb was the rare disorder

methylmalonic aciduria.(Milunsky, 1989). This disorder causes failure to thrive,

vomiting, lethargy, biochemical disturbances, poor muscle tone, and eventually

mental and motor retardation. Treatment of the fetus through the mother during

pregnancy is carried out by giving her intramuscular injections of massive doses

of vitamin B12. This method secures the child’s health at birth, when a special

low-protein diet is started. In this way serious illness, mental retardation

and early death have been averted.

Another considerably more common disorder is congenital adrenal

hyperplasia (CAH). This heredity disorder is inherited equally through a gene

from both parents (autosomal recessive). About 1 in 5,000 to 13,000 whites and

1 in 7550 Japanese are born with CAH – nowhere near the remarkable 1 in 282

among the Yupik Eskimos. (Jones, 1988). Various forms of this disorder occur,

each due to a deficient, though different enzyme along a stepwise pathway that

finally results in the production of “cortisone”. Symptoms of the most common

form of CAH are masculinization of the female genitals, excessive growth, early

appearance of pubic hair, and enlargement of the penis or clitoris. Critically

important in about two-thirds of affected children is the occurrence of a life-

threatening crisis one to four weeks after birth, characterized by vomiting,

diarrhea, and salt loss leading to collapse and even death if not diagnosed and

treated with “cortisone”. Where needed, surgical correction of the female

genitals is possible, and normal growth, puberty and fertility can be achieved

through lifelong medical treatment with cortisone like supplements. Today, both

carrier detection and prenatal diagnosis are possible for most families, using

DNA techniques combined with special blood-group linkage studies.

The very first inherited biochemical disorder found to cause mental

retardation was phenylketonuria.(Koiata, 1995). Since that description in 1934,

it has been learned that PKU (phenylketonuria) occurs in about 1 in 14,000

newborns in the United States and as frequently as 1 in 4,500 in Northern

Ireland.( Nora, 1989). Transmitted by a recessive gene from each parent, all

problems are the result of a deficient liver enzyme. An affected untreated

child will develop irreversible mental retardation. Therefore, in most Western

countries , blood screening of newborns is done to make an immediate diagnosis

and institute the special low-protein diet through which mental retardation can

be avoided.

Despite the availability of effective treatment after birth, prenatal

diagnosis remains a serious option for parents. This option is valuable because

the special low protein diet is tasteless and very restrictive.(Mulinsky, 1989).

Enforcing the diet in early childhood is difficult, and needs to be continued

for as long as possible. (Mulinsky, 1989). The usual practice has been to

discontinue the diet at four to seven years of age. Recent studies show

intellectual deterioration, loss of IQ pionts, learning difficulties, and

behavior problems after the diet has been discontinued. (Jones, 1988). A

steadily increasing number of women with PKU are entering the childbearing years.

(Jones, 1988). If they become pregnant, the chemical products that accumulate

in their blood damage the fetal brain and other developing organs. Their risk

of having a retarded child or one with a heart defect or microcephaly approaches

an incredible 100 percent. (Koiata, 1995). Only a mere handful of cases are

known in which the diet was adhered to strictly before conception and a healthy

child is born. Today, new DNA techniques have made both carrier detection and

prenatal diagnosis of PKU possible for most families and therefore an important

decision.(Koiata, 1995).

Galactosemia is another treatable hereditary biochemical disease where

prenatal diagnosis is possible. If the fetus is affected, special lactose-free

dietary treatment of the mother started early enough will almost always avert

early death or mental retardation, cataracts, and liver damage.(Jones, 1988).

There are a few other very rare disorders where prenatal diagnosis and early

treatment may be critical to save life or prevent mental retardation or other

consequences. Some of these diseases are: tyrosinemia, homocystinuria, maple-

sirup urine disease, and propionicacidemia. (Jones, 1988). A few other

disorders are now being conquered by early diagnosis and treatment in the womb.

(Jones, 1988). Continued support for medical research will undoubted provide

more and more opportunities for early treatment or prevention, reducing the need

for abortion, which is a major option and issue today. Progress in actual

prenatal treatment for genetic disorders can be anticipated, provided that fetal

research is not interdicted by state legislation. (Nora, 1989).

The fact that mental retardation is more common in males has been a

known fact for about a century. (Emery, 1968). The major reason for this excess

became clear in the mid-1970’s, when studies from Australia focused attention on

an unexpectedly common disorder with striking features: the fragile -X syndrome.

(Nora, 1989). This disorder, caused by a single defective gene on the X

chromosome, has highly variable signs that usually include mental retardation

and distinctive facial features. (Milunsky, 1989). Special studies have

revealed the location of the defective gene on the X chromosome: a vulnerable

spot that tends to break, hence, the term “fragile-X syndrome.” (Milunsky, 1989).

Because of the remarkable variability of the physical, behavioral, and

developmental features of fragile-X syndrome and the delayed appearance of some

major features, definitive recognition of this disorder eluded researchers for

many years. (Milunsky, 1989). Confusion was also generated by the fact that

although males were primarily affected, within the same families mildly affected

females were also observed. It is now known that about 1 in 1,060 males are

born with fragile-X syndrome, and that the disorder accounts for about 25

percent of all male cases of mental retardation and about 10 percent of mild to

moderate mental retardation in females.(Nora,1989). The main signs of this

disorder are on Table 1.

Transmission of the fragile-X disorder was initially thought to conform

to other sex-linked disorders. Quite unexpectedly, a unique pattern that does

not conform exactly to sex-linked inheritance has been discovered only recently.

The current knowledge, as studied by Dr. Milunsky, allows certain risk


1. An intellectually normal female who inherits the fragile-X gene from

her carrier mother has a 50 percent risk of having an affected son, whose risk

of being retarded is 40 percent . Half her daughters will carry the gene, but

only 16 percent will be retarded.

2. If such a daughter is retarded, her risk of having an affected and

retarded son is 50 percent. If she has a daughter herself, the risk is 28

percent that the will also be mentally impaired.

3. Men who are seemingly entirely normal and do not even show the

fragile-X chromosome when tested may nevertheless transmit the gene to all their

daughters. These females are usually intellectually normal. However, when they

reproduce, 50 percent of their sons will be affected, and 40 percent will be

retarded. Half their daughters will be carriers, among 16 percent will be


4. Normal-but-transmitting males may account for 20 percent of all cases

of the fragile-X syndrome. Unfortunately, they will remain undetectable until

new technology revels their ominous burden or until one of their children or

grandchildren is diagnosed as having this fateful flaw.

5. Curiously, women carriers who bear a son who is a normal-but-

transmitting male have a 50 percent risk of having an affected male, who has

only a 9 percent risk of being retarded. This carrier female also has a 50

percent risk of having carrier daughters, and these girls have only a 5 percent

risk of being intellectually impaired.

Further research inth this devistating disorder and it’s complex

heridaty pattern may significantly reduce the amount of congenital mental


Heredity, biochemical and other disfiguring birth defects must be a top

priority with expectant parents. A knowledge of these concerns will alolow them

to make wise decisions regarding prenatal diagnosis and decisions and

availability of treatment to prevent birth defects, thereby saving lives.


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