Question

A 32-year-old Caucasian man underwent testing for Huntington’s Disease. The patient was a lively and talkative child who completed high school with As and Bs and college with poor grades. At age 22 he became quiet and non-conversant. At age 24 he began work as a cook/dishwasher and displayed noticeable un-coordination. At age 28 he developed dysarthria, dysphagia, stiffness, slow ataxic gait, and dementia. There was no history of schizophrenia or depression and the neurological review of systems was negative. Both parents were in their late 60s and in excellent health, without signs of dementia. There was no history of any neurodegenerative disease and he had three sisters, aged 35-37, all in good health.

Laboratory Results:

Creatine phosphokinase: Normal

Vitamin E: Normal

Lactate: Normal

Pyruvate: Normal

Imaging Results:

MRI: Generalized, cerebral and cerebellar atrophy

​​Very mall caudate nuclei

HIstology Results:

Skin biopsy: Normal mitochondria

Bone Marrow and Enzyme Screen:

Human Granulocyte-Macrophage: Normal

Metachromatic Leukodystrophy: Normal

Krabbe’s disease: Normal

Physical examination:

Mini-mental status exam: 20/26

Cranial nerve exam: decreased upgaze, saccadic extraocular eye movement, dysarthria and hyperactive gag reflex

Strength: Normal

Gait: wide-based and ataxic

Molecular Test Results:

Diagnostic HTT molecular test for patient:

​​​1 band representing 23 CAG repeats

​​​1 band representing 49 CAG repeats

HTT molecular test for father:

​​​1 band representing 20 CAG repeats

​​​1 band representing 37 CAG repeats

HTT molecular test for mother:

​​​1 band representing 17 CAG repeats

Predictive HTT molecular test for sister:

​​​1 band representing 17 CAG repeats

​​​1 band representing 20 CAG repeats

1. What testing methodology would be used to evaluate the repeat sizes for the patient and the family?

2. If he has a child that is affected, would you expect the age of onset to be earlier or later and repeats to be approximately the same, less, or expanded? What is the term to describe this phenomenon?

Answer 1

Ans-

Based on the symptoms, The underlying disorder can be Parkinsons disease. No specific test exists to diagnose Parkinson's disease. Your doctor trained in nervous system conditions (neurologist).

Huntington's disease is an inherited disease that causes the progressive breakdown (degeneration) of nerve cells in the brain. Huntington's disease has a broad impact on a person's functional abilities and usually results in movement, thinking (cognitive) and psychiatric disorders.

Most people with Huntington's disease develop signs and symptoms in their 30s or 40s, but the onset of disease may be earlier or later in life. When disease onset begins before age 20, the condition is called juvenile Huntington's disease. Earlier onset often results in a somewhat different presentation of symptoms and faster disease progression.

The talkative child are change into quite and unconditional because of Parkinson's disease.Parkinson's and Huntington's affect movement.

1)The Huntington's disease are possitive for father, so chances to caused in son by genetic,or inherited way.this transfer from father to child by genes,so methodology used for dignostic purpose is Genetic test for dignosis of disease.

Genetic test-

Used for repeat results.genetic test can be given to someone who has a family history of the disease but shows no signs or symptoms. This is called predictive testing. The test result has no treatment benefit, and it doesn't indicate when disease onset will begin or what symptoms are likely to appear first.

Some people may elect to do the test because they find it more stressful not knowing. Others may want to take the test before they make decisions about having children.

Risks may include problems with insurability or future employment and the stresses of facing a fatal disease. These tests are only performed after consultation with a genetic counselor.

The discovery of the HD gene led to a genetic test to make or confirm the diagnosis of Huntington's disease. Using a blood sample, the genetic test analyzes DNA for the HD mutation by counting the number of CAG repeats in the huntingtin gene. Individuals who do not have HD.

positive or negative genetic test result for HD is 98-99% accurate. The genetic test is not absolutely 100% accurate because of the possibility of human or technical error that is unavoidable in laboratory procedures.

2) Transfer of disease from father to child and child suffering from disease in early stage called as juvenile Huntington's disease.this occurr before age of 20 years.

Child is suffering from same problem as father as earlier.age on onset to be earlier.Typically, HD symptoms appear in middle age. But with juvenile Huntington’s disease (JHD), symptoms begin in childhood. In addition to the symptoms of the adult disease, early signs in children may include seizures and stiffness. Children with JHD most often inherit the disease from their fathers.

Age on Onset in child is earlier and repeats to be expanded.