Bread n' Butter (Psychopharm)
Which one of the following antidepressants does not have strong sedative effects?
A. Trazodone
B. Paroxetine
C. Doxepin
D. Clomipramine
E. Mirtazapine
B
The TCAs, trazodone, and mirtazapine are all sedating drugs. Sedation is a common effect of the TCAs and can be a welcome one if the patient isn’t sleeping well. The most sedating of the TCAs are amitriptyline, trimipramine, and doxepin. The least sedating are desipramine and protriptyline, with other TCAs falling between these two groups in the amount of sedation they cause. Trazodone is an antidepressant that can be extremely sedating. For this reason, it is sometimes used independently for insomnia. Trazodone can also cause priapism, in which case the patient should be switched to another medication. The SSRIs and the serotonin and norepinephrine reuptake inhibitors in general are not very sedating.
How long after taking PCP can it still be found in the urine?
A. 1 day
B. 2 days
C. 5 days
D. 8 days
E. 10 days
D
PCP can be found in the urine up to 8 days after use. Some other drugs of note include cannabis, up to 4 weeks; cocaine, up to 8 hours; and heroin, up to 72 hours.
The drainage of CSF into the blood is a function of the:
A. Choroid plexus
B. Virchow–Robin spaces
C. Dural mitochondria
D. Ventricular ependymal cells
E. Arachnoid granulations
E
The arachnoid granulations are the major sites for drainage of CSF into the blood. These granulations protrude through the dura into the superior sagittal sinus and act as one-way valves or siphons for the CSF. Equilibrium is maintained by the arachnoid granulations, for if the CSF pressure drops below a certain level, absorption stops. If the CSF pressure increases, more fluid is absorbed. The choroid plexuses that protrude into the ventricles are responsible for the majority of CSF production in humans. In humans, the rate of CSF production is about 0.35 mL/min. Drugs that can temporarily reduce production of CSF and ease increased intracranial pressure include acetazolamide and mannitol. States of hypothermia, hypocarbia, hypoxia, and hyperosmolality can also temporarily decrease CSF production. Virchow–Robin spaces act as a duct for substances in the subarachnoid space to enter the brain. The other answer choices are distractors.
A team comprising a psychiatrist, psychologist, social worker, nurse, and medical student discharges a patient because the insurance will no longer pay for her stay. She commits suicide. Who will be held legally responsible for the team’s actions?
A. The medical student
B. The psychologist
C. The social worker
D. The nurse
E. The psychiatrist
E
The psychiatrist is the member of the team who is held legally responsible for the team’s decisions. It stems from the concept that the highest person in the hierarchy is responsible for the actions of those he or she supervises. The psychiatrist is considered the head of this team. As such, the attending psychiatrist is responsible for the actions of the residents he or she supervises and is responsible for the actions of the team.
Which one of the following is not a DSM criterion for schizophrenia?
A. Delusions
B. Presence of active-phase symptoms for 6 months
C. Hallucinations
D. Disorganized speech
E. Grossly disorganized or catatonic behavior
B
To diagnose schizophrenia, active-phase symptoms must be present for a 1-month period only. It may be diagnosed if other symptoms (i.e., negative) are present over a 6-month period, but active-phase symptoms must be present for at least 1 month of those 6 months. All other answer choices are part of the characteristic active-phase symptoms for schizophrenia. Social isolation is a bad prognostic sign for schizophrenia. Good prognostic signs include late age of onset, acute onset, and the presence of an affective component.
You are called to consult on an agitated patient in the medical unit. The patient is elderly and confused and is pulling out her I.V. lines. You decide that she must be tranquilized for her own safety. Which one of the following drugs would be the best choice?
A. Lorazepam
B. Lithium
C. Esketamine
D. Aripiprazole
E. Haloperidol
E
The best choice for tranquilizing agitated patients is haloperidol. Given that the patient in question is elderly, starting with a small dose of haloperidol would be appropriate. Benzodiazepines should be avoided in cases of suspected delirium, which based on the question stem, is a concern for this patient. Hence answer choice A is out. A benzodiazepine given to a delirious patient can worsen the delirium and further disinhibit the patient, making him or her more agitated. In general one should use great caution in giving benzodiazepines to the elderly, and when used, they should be given in small doses. Esketamine is a nasal spray derived from ketamine, which is sold in the U.S. under the name Spravato, and is indicated for treatment of treatment-resistant depression. It is a N-methyl-D-aspartate (NMDA) receptor antagonist, has potential for abuse and dissociative symptoms, and is monitored by a risk evaluation and management program similar to clozapine. Aripiprazole, an atypical antipsychotic, comes only in oral form, which would probably be unfeasible for an acutely agitated patient. Other atypical antipsychotic drugs that come in intramuscular injectable form, such as olanzapine or ziprasidone, would be appropriate choices. Lithium is not standardly used to tranquilize patients. It is a mood stabilizer used in the treatment of bipolar disorder and can be administered only orally.
A 20-year-old college student is brought into the emergency room after a party. He has tenting of the skin on the backs of his hands, is nauseated and vomits, acts seductively toward the nursing staff, and thinks the security guards are out to kill him. He tells you: “The one with the red hair is out to slay me.” The emergency medical technician tells you the patient apparently collapsed while dancing at a “rave.” What substance has he most likely taken?
A. Cannabis
B. Ketamine
C. Diacetylmorphine
D. Methylenedioxyamphetamine
E. Some form of volatile inhalant
D
Methylenedioxyamphetamine (MDMA) is also known as ecstasy. It is in the amphetamine family and is a common drug of abuse at clubs and raves. Symptoms of intoxication with amphetamines include euphoria, changes in sociability, hypervigilance, changes in interpersonal sensitivity, anxiety, anger, and impaired judgment. Amphetamines can induce a psychosis that includes paranoia, hyperactivity, and hypersexuality. Physical effects include fever, headache, cyanosis, vomiting (leading to dehydration), shortness of breath, ataxia, and tremor. More serious effects can include myocardial infarction, severe hypertension, and ischemic colitis. Cannabis intoxication presents as impaired coordination, euphoria or anxiety, sense of slowed time, social withdrawal, and impaired judgment. Physical signs include conjunctival injection, increased appetite, tachycardia, and dry mouth. Ketamine is a relative of PCP. Intoxication presents as belligerence, impulsivity, psychomotor agitation, and impaired judgment. Physical signs include nystagmus, hypertension, ataxia, dysarthria, or muscle rigidity. Psychosis may be present and can persist for up to 2 weeks after intoxication. Diacetylmorphine is heroin. Intoxication results in euphoria followed by apathy, psychomotor agitation or retardation, impaired judgment, pupillary dilation, sedation, slurred speech, and impaired attention or memory. Volatile inhalant intoxication presents as belligerence, assaultiveness, apathy, impaired judgment, dizziness, nystagmus, impaired coordination, unsteady gait, lethargy, tremor, psychomotor retardation, muscle weakness, euphoria, or coma. Low doses of these substances can cause feelings of euphoria. High doses can cause paranoia, fearfulness, and hallucinations.
Pure motor hemiparesis is most likely to result from a stroke localized to the:
A. Midbrain
B. Cerebellum
C. Medulla
D. Thalamus
E. Internal capsule
E
Pure motor hemiparesis is one of the classic lacunar stroke syndromes and would be expected from an infarct in the area of the internal capsule, the basis pontis, or the corona radiata. Lacunar strokes are characterized as ischemic strokes resulting from small-vessel lipohyalinosis, for which hypertension and diabetes are the two major risk factors. Lacunar infarcts by definition are small and range from 0.5 mm to 1.5 cm in diameter. Microembolism may also be a mechanism of lacunar strokes.
Other lacunar syndromes include pure sensory stroke, resulting usually from a small lesion in the ventro-posterolateral nucleus of the thalamus; sensorimotor stroke, resulting from a stroke to the internal capsule and thalamus or the posterior limb of the internal capsule; ataxic hemiparesis, which results from a lacunar infarct to either the basis pontis or the posterior limb of the internal capsule; and the dysarthria–clumsy hand syndrome, resulting from a stroke to the deep areas of the basis pontis.
Which ruling determined that the physician–patient relationship imposes an obligation on the psychiatrist for care and safety of the patient and others?
A. Wyatt v Stickney
B. Durham v the United States
C. O’Connor v Donaldson
D. Tarasoff v Regents of the University of California
E. Clites v State
D
Tarasoff v Regents of the University of California is the landmark case from 1976 in which the California Supreme Court ruled that any psychotherapist who believes that a patient could injure or kill someone must notify the potential victim, the victim’s relatives or friends, or the authorities. In 1982 the same court issued a second ruling that broadened Tarasoff to include the duty to protect, not only to warn, the intended victim.
The Durham Rule was determined by the ruling in the case of Durham v the United States in 1954 by Judge Bazelon. This rule stipulates that a defendant cannot be found criminally responsible if the criminal act was the product of a mental illness or defect. In 1972 the District of Columbia Court of Appeals, in the ruling United States v Brawner, discarded the Durham Rule.
In 1976 in the ruling of O’Connor v Donaldson, the U.S. Supreme Court ruled that harmless mentally ill patients cannot be confined involuntarily without treatment if they can survive outside an institution.
Clites v State of Iowawas a landmark case pertaining to a ruling in favor of a patient and his family, who sued for damages resulting from chronic neuroleptic exposure that resulted in tardive dyskinesia. The appellate court ruled that the defendants deviated from the usual standards of care by failing to conduct physical examinations and routine laboratory tests and failed to intervene at the first signs of tardive dyskinesia.
Which one of the following does not describe a patient with attention deficit hyperactivity disorder (ADHD)?
A. The patient fails to follow through on instructions and fails to finish schoolwork
B. The patient often fidgets with hands or feet or squirms in his or her seat
C. The patient often has difficulty awaiting his or her turn
D. The patient often seems not to listen when spoken to directly
E. The patient shows impairment from symptoms at school but not at home
E
ADHD is diagnosed by six or more symptoms of inattention or six or more symptoms of hyperactivity–impulsivity that persist for 6 months or more. Several inattentive or hyperactive–impulsive symptoms should be present before age 12. Several symptoms of impairment must be present in more than one setting to make the diagnosis. Symptoms of inattention involve failure to pay close attention to tasks, failure to sustain attention, not listening, not following through on tasks, problems organizing tasks, forgetfulness, and being easily distracted by extraneous stimuli. Symptoms of hyperactivity–impulsivity include fidgeting, inability to remain seated when expected, running or climbing excessively, difficulty playing quietly, acting as if driven by a motor, talking excessively, blurting out answers, difficulty awaiting turn, and interrupting others.
Patients who smoke tobacco heavily can markedly reduce levels of psychotropic medications they are taking. Which one of the following medications is not affected by tobacco smoking in this way?
A. Clozapine
B. Olanzapine
C. Haloperidol
D. Risperidone
E. Amitriptyline
D
Tobacco smoking is a potent inducer of CYP 1A2. As such, it can significantly lower levels of amitriptyline, fluvoxamine, clozapine, olanzapine, haloperidol, and imipramine. Risperidone is a substrate of CYP 2D6, and its levels can be lowered by 2D6 inducers, such as dexamethasone and rifampin. Risperidone levels can be significantly increased by 2D6 inhibitors, such as bupropion, citalopram, clomipramine, doxepin, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline, and perphenazine. Risperidone levels are not affected by tobacco smoking.
A patient asks you about the data proving that alcoholism is hereditary. During your discussion, the patient asks you the following question: “The study of which group most strongly supports the heredity of alcoholism?” The correct answer is:
A. Siblings
B. Cousins
C. Parents
D. Mothers–daughters
E. Adopted siblings
E
There are multiple studies that all point to a genetic predisposition for alcoholism. The studies that separate environmental from genetic factors are some of the most convincing. Studies of adoptees clearly demonstrate that children whose biological parents were alcoholics are at increased risk for alcoholism, even when brought up by adopted families in which neither parent has an alcohol problem. In addition, children whose biological parents do not have an alcohol problem are not more likely to become alcoholic if raised in a home with parents who have alcohol problems
The primary auditory cortex localizes to which one of the following brain regions?
A. Temporal lobe
B. Parietal lobe
C. Frontal lobe
D. Occipital lobe
E. Thalamus
A
The primary auditory cortex localizes to the superior temporal gyrus (Heschl’s gyrus) in both temporal lobes. Cortical deafness can result from bilateral strokes to the temporal lobes that destroy Heschl’s gyri. The thalamus is of course the relay station for much of the sensory input to the brain. The frontal lobes are responsible for attention, concentration, set-shifting, organization and executive functioning, and planning. The occipital lobes are the location of the calcarine cortex, which is responsible for interpreting and processing visual input and stimuli.
Which one of the following is not necessary for a patient to be declared competent to stand trial?
A. Understanding of the nature of the charges against him or her
B. Not having a mental illness
C. Having the ability to consult a lawyer
D. Helping the lawyer in his defense
E. Understanding of court procedure
B
In the case of Dusky v United States, the U.S. Supreme Court determined that to have the competence to stand trial, a criminal defendant must be able to have the ability to consult his or her lawyer with a reasonable degree of rational understanding, and he or she must have a reasonable and rational under-standing of the proceedings against him or her. The McGarry instrument is a clinical guide that identifies 13 areas of functioning that must be demonstrated by a criminal defendant to be declared competent to stand trial. Answer choices A, C, D, and E are included in these 13 areas, as well as the ability to plan legal strategy, ability to appraise the roles of participants in courtroom procedure, capacity to challenge prosecution witnesses realistically, capacity to testify relevantly, ability to appraise the likely outcome, and understanding the possible penalties, among several others.
A patient comes to your clinic with complaint of hypersomnia, hyperphagia, psychomotor slowing, and depressed mood. He states that this happens yearly, usually around October or November. The treatment plan for this man should include:
A. Risperidone
B. Naloxone
C. Exposure to bright artificial light for 2 to 6 hours per day.
D. Flooding
E. Alprazolam
C
This is a case of SAD, which is a depression that sets in during the fall and winter and resolves during the spring and summer. It is often characterized by hypersomnia, hyperphagia, and psychomotor slowing. Treatment involves exposure to bright artificial light for 2 to 6 hours each day during the fall and winter months. It is thought to be related to abnormal melatonin metabolism. All other answer choices given are distractors and are unrelated to the patient’s primary problem
A 16-year-old male suffers from irritable mood, increased energy, decreased need for sleep, and pressured speech. He was recently started on medication by his psychiatrist to control these symptoms. He comes into your office complaining of a significant worsening of his acne since starting this new medication. What drug was he started on?
A. Oxcarbazepine
B. Cariprazine
C. Risperidone
D. Lithium
E. Lamotrigine
D
Several cutaneous side effects are possible with lithium, including acne and follicular and maculopapular eruptions. Lithium can both cause and exacerbate psoriasis. Alopecia has also been reported. Major side effects of lithium include gastrointestinal complaints, tremors, diabetes insipidus, hypothyroidism, weight gain, cardiac arrhythmia, and edema. Frequently tested is the fact that in patients suffering from psoriasis, lithium can precipitate psoriasis flare-ups. Another high-yield fact about lithium is that lithium decreases the kidney’s ability to respond to antidiuretic hormone (ADH), resulting in decreased fluid resorption from the distal tubules and increased urine output. Lamotrigine is an anticonvulsant that is also used for mood stabilization. Side effects can include Stevens–Johnson syndrome, anemia, thrombo-cytopenia, liver failure, and pancreatitis. Cariprazine is an atypical antipsychotic sold in the U.S. under the brand name Vraylar, with indications for schizophrenia and bipolar disorder. It can cause extrapy-ramidal symptoms, neuroleptic malignant syndrome, and akathisia, among other effects. Risperidone is an antipsychotic that can cause extrapyramidal side effects, neuroleptic malignant syndrome, metabolic syndrome, gastrointestinal upset, increased salivation, and lactation, among other effects. Oxcarbazepine is an anticonvulsant that may cause leukopenia, thrombocytopenia, Stevens–Johnson syndrome, and several other side effects. With the exception of lithium, the other choices do not worsen acne.
A young patient presents to your office with dementia. He has been involved in heavy drug use. He has used heroin, PCP, lysergic acid (LSD), amphetamines, and inhalants. If you were to postulate which most likely caused his dementia, which one would you choose?
A. Heroin
B. LSD
C. PCP
D. Amphetamines
E. Inhalants
E
Inhalants can cause a persisting dementia. It is irreversible, except for the mildest cases. It may be the result of the neurotoxic effects of the inhalants, the metals they contain, or the effects of hypoxia. Inhalant use can also lead to delirium, psychosis, and mood and anxiety disorders. Signs of intoxication with inhalants include maladaptive behavior, such as assaultiveness; impaired judgment; and neurological signs, such as dizziness, slurred speech, ataxia, tremor, blurred vision, stupor, and coma. The other answer choices have various effects but do not cause a persisting dementia. One of our answer choices is LSD. Keep in mind that LSD is thought to work as a partial agonist at postsynaptic serotonin receptors. LSD use therefore alters postsynaptic serotonin binding. This is a useful little fact for the standardized test taker to know.
Which one of the following is not an appropriate therapy for status epilepticus?
A. Rectal diazepam
B. Intravenous lorazepam
C. Intramuscular phenytoin
D. Intravenous valproic acid
E. Oxygen by nasal cannula with airway protection
C
Intramuscular phenytoin is a poor choice for treatment of status epilepticus because of its erratic rate of absorption. Useful status epilepticus treatments include rectal or intravenous diazepam, intravenous lorazepam, intravenous phenytoin or fosphenytoin, intravenous valproic acid, oxygen by nasal cannula and airway protection, and intravenous phenobarbital. Phenobarbital is acceptable treatment but not the best choice because of the narrow therapeutic window and possibility of overdose leading to respiratory depression and possible death.
A consultation-liaison psychiatrist is called to evaluate a patient who is in denial of a major illness. The most important obligation of the psychiatrist at the first evaluation is to:
A. Confront the denial forcefully
B. Tell the staff to “play along” with the patient’s denial
C. Obtain neuropsychological testing
D. Meet with the patient’s family
E. Make sure the patient has been informed about the illness and treatment
E
One cannot treat what is assumed to be denial before actually knowing that it is denial. Often in medical settings things are not clearly explained to patients in language they can understand. As such, it is first necessary to explain what is going on to the patient clearly and in language he or she can follow. Confronting the patient’s denial forcefully, and aggressively removing his or her defenses against overwhelming emotion, is potentially more harmful than helpful. Playing along with the denial can lead to noncompliance and failed treatment outcomes and is a bad idea. Neuropsychological testing is not necessary if a patient is in denial. If the patient had a neurocognitive deficit that precluded his or her understanding of the material as presented it could be considered, but those were not the circumstances described in this question. Meeting the family is important, but not more important than making sure the patient has had the situation explained properly. The patient is the primary person who has to understand. Informing the family while the patient is left in the dark is not the best approach.
How is a doctor who agrees to take Medicare paid?
A. He or she agrees to take only what Medicare pays for the service
B. He or she is allowed to bill the patient for the difference between what Medicare pays and what he or she charges
C. He or she is paid by a third party to make up the difference between the fee-for-service rate and the fee allowed by Medicare
D. He or she can sue the government if the full fee is not paid
E. He or she is not allowed to charge copays
A
The doctor who takes Medicare must accept Medicare’s maximum fee. This fee includes any appropriate co-pays set forth in the patient’s policy. The physician cannot bill the patient or another party for the difference between what Medicare allows and what the physician wants to charge.
Which one of the tricyclic antidepressants has the most antihistaminic activity?
A. Amoxapine
B. Clomipramine
C. Desipramine
D. Nortriptyline
E. Doxepin
E
Doxepin is the tricyclic with the most antihistaminic activity.
Which one of the following substances of abuse is the most likely to lower the seizure threshold during intoxication?
A. Morphine
B. PCP
C. Cocaine
D. Cannabis
E. Alcohol
C
Stimulants such as cocaine typically lower the seizure threshold when abused to intoxication. In moderate doses, cocaine and the stimulants can produce wakefulness, alertness, mood elevation, diminished appetite, and increased performance in certain tasks. The stimulants can also result in psychosis and paranoia. There is also an increased risk of myocardial infarction with cocaine use. Systemic problems such as dehydration, rhabdomyolysis, and hyperthermia can also be noted. The most common neurologic adverse effect of cocaine and the stimulants is headache. In certain cases, the stimulants can produce myoclonus, encephalopathy, and seizures. Cocaine is the stimulant that is most likely to induce seizures. Smoking and intravenous administration of cocaine are more likely to induce seizures than intranasal use. Ischemic and hemorrhagic strokes can also result from cocaine use. Cocaine is the most significant cause of drug-induced stroke and accounts for about 50% of all cases. The mechanism of cocaine-induced stroke is believed to involve vasoconstriction, acute hypertension, and vasospasm.
Opioid ingestion and intoxication can produce a state of euphoria or dysphoria. Other possible adverse effects include hallucinations, dry mouth, nausea, vomiting, constipation, and urinary retention. Examination usually reveals pupillary constriction during acute intoxication. Autonomic disturbance, such as hypotension and hypothermia, can also be noted. Seizures are rare with opioid intoxication. Overdose can result in coma and respiratory compromise. Opioids do not usually cause seizures or lower the seizure threshold.
PCP intoxication produces hallucinosis, dysphoria, and paranoia. Agitation, catatonia, and bizarre behavior are also common. At higher doses, PCP use can lead to stupor and coma. In overdose, rhabdomyolysis may result from agitation and dysautonomia, such as fever, hypertension, and sweating. PCP can lower the seizure threshold, but less frequently than cocaine.
Tetrahydrocannabinol (THC), the primary active ingredient in marijuana, causes euphoria, depersonalization, and relaxation. Other effects of the drug include sleepiness, paranoia, and anxiety. High doses of THC can result in hallucinosis, panic, and even paranoia. Seizures are not generally noted with THC intoxication.
Alcohol has intoxicating effects that can cause sedation, memory impairment, uncoordination, dysarthria, euphoria, dysphoria, sleepiness, and acute confusion. Alcohol intoxication does not lower the sei-zure threshold; it, in fact, is protective against seizures because of its agonistic effects at the GABA-A receptor. Alcohol withdrawal can lower the seizure threshold because of rapid desaturation of the GABA-A receptor, in much the same way as the benzodiazepines.
Which one of the following is not more typical of a cortical dementia than of a subcortical dementia, such as dementia of the Alzheimer type?
A. Apathy and depression
B. Aphasia
C. Dyspraxia
D. Absence of motor abnormalities
E.vInsidious progression of cognitive decline
A
The cortical dementias, such as Alzheimer’s disease, generally produce a gradual decline in cognitive function with normal cognition speed and the presence of aphasia, dyspraxia, and agnosia. Depression is less common in cortical dementia than in subcortical disease. Motor abnormalities are typically absent in cortical dementia, unless the disease is in the terminal stages. Subcortical dementia, as exemplified in Parkinson’s disease, typically presents with dysarthria and extrapyramidal motor abnormalities. Apathy and depression are often present. Frontal memory impairment with recall aided by cues is often noted. Speed of cognition in subcortical dementia is slow.
Which one of the following is false concerning the right to die and surrogate decision making?
A. Patients who believe that continuing treatment would lessen their quality of life have the right to demand that treatment be withheld or withdrawn
B. Advanced directives or a living will is a way for patients to express their preferences before anything happens that would cause them to lose capacity
C. If a patient leaves no clear instructions, the state will carry out a course of action to protect and preserve human life
D. Surrogate decision makers can be appointed by the patient or the courts
E. The standard of substituted judgment means that the surrogate will do whatever is in the patient’s best interests
E
The standard of substituted judgment holds that a surrogate decision-maker will make decisions based on what the patient would have wanted and implies that the decision-maker be familiar with the patient’s values and attitudes. The best interest principle, which was the past but not current standard, states that a decision-maker will decide which option would be in the patient’s best interests. Patients do have the right to refuse treatment that they feel would lessen their quality of life. Advanced directives and living wills are ways for patients to preserve their wishes in writing so that their desires are reflected in the decisions that are made for them should they become incapacitated. The state will follow the course that preserves human life should a suitable surrogate decision-maker not be present. Surrogate decision-makers can be appointed by the patient, the court, or the hospital. In many cases this person is the patient’s next of kin.
A 13-year-old boy is brought to the emergency room from a group home because of acute agitation. On examination you note choreoathetotic movements, hyperreflexia, acute agitation, self-scratching and mutilating behavior, and marked cognitive impairment. You peruse the group-home chart and note that this young boy has an enzymatic deficiency in hypoxanthine–guanine phosphoribosyltransferase. Your keen memory brings you back to your pediatrics rotation in medical school, and you realize the diagnosis is:
A. Tay–Sachs disease
B. Metachromatic leukodystrophy
C. Krabbe’s disease
D. Gaucher’s disease
E. Lesch–Nyhan syndrome
Lesch–Nyhan syndrome is an X-linked recessive hereditary disorder of purine and pyrimidine metabolism. Hyperuricemia results from a deficiency in hypoxanthine–guanine phosphoribosyltransferase. Clinical symptoms and signs of the syndrome include choreoathetosis, hyperreflexia, hypertonia, dysarthria, behavioral disturbances, cognitive impairment, and self-mutilatory behavior. Neurologic signs and symptoms are probably a result of diminished dopamine concentrations in the CSF and basal ganglia.
Metachromatic leukodystrophy is an autosomal recessive disorder caused by arylsulfatase A deficiency. There is an accumulation of excess sulfatides in the nervous system, which leads to progressive demy-elination. The disorder localizes to chromosome 22.
Tay–Sachs is a recessive disorder localizing to chromosome 15. It is caused by a deficiency in hexosaminidase A. The adult form presents as progressive weakness in the proximal muscles of the upper and lower extremi-ties. Associated symptoms may involve spasticity, dysarthria, and cognitive and psychiatric impairment.
Krabbe’s disease, also called globoid cell leukodystrophy, is an autosomal recessive disease that local-izes to chromosome 14. It is a result of a deficiency in the lysosomal enzyme galactocerebroside β-galactosidase. Generalized central and peripheral demyelination is the hallmark of the disorder, as is the presence of multinucleated macrophages (globoid cells) in cerebral white matter. Infantile arrest of motor and cognitive development is noted, with seizures, hypertonicity, optic atrophy, and opisthotonic posturing (extension of trunk and limbs with increased muscle tone) occurring. Stem cell transplantation may reverse the neurologic deficits by providing the missing enzyme.
Gaucher’s disease is an autosomal recessive disorder resulting from β-glucosidase deficiency. It localizes to chromosome 1. There are three identified types. Type I presents with the characteristic findings of hematologic anomalies, hypersplenism, bone lesions, skin pigmentation, and ocular pingueculae (growth on the conjunctiva).