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From the presentation given at the National Coalition for PKU and Allied Disorders Metabolic Conference in Ohio in May 2001.

On Saturday, Kevin M. Antshel, Ph.D., a fellow in Pediatric Neuropsychology, Children's Hospital in Boston, and holder of an appointment from Harvard Medical School through the Department of Psychiatry, spoke to the entire group about the prevalence of ADHD in metabolic disorders. He presented an overview of ADHD, discussed ADHD and metabolic disorders, explained courses of action that can be taken if a child has ADHD, and told about the resources available for parents whose children have been diagnosed with the disorder.

The terminology of the disorder has changed over the years. In the late forties, it was known as Strauss Syndrome, later Minimal Brain Damage, and still later, Hyperkinesis. By the eighties, it had become Attention Deficit Disorder with or without hyperactivity and residual type. In 1987, it was shortened to Attention Deficit Hyperactivity Disorder (ADHD). By 1994, three subtypes of the disorder were recognized - ADHD-Hyperactivity/ impulsive type (ADHD-H), ADHD-Inattentive type (ADHD-I) and ADHD-Combine type (ADHD-C).

There are certain criteria for a diagnosis of ADHD:

  1. There must be a persistent pattern of inattention and/or hyperactivity.
  2. The symptoms must be present before the age of 7 and have lasted at least six months.
  3. The symptoms must have been observed in at least two settings, such as home and school.
  4. The symptoms must be severe enough to clearly interfere with developmentally appropriate functioning.
  5. The disturbance does not occur exclusively during the course of:
    1. Developmental disorders (such as mental retardation).
    2. Schizophrenia or other psychotic disorders.
    3. It cannot be better accounted for by another psychological disorder such as mood or anxiety disorders.

The symptoms that differentiate the subtypes are:

  1. Hyperactivity/impulsivity produces a peculiar behavior pattern where the child
    1. Fidgets and squirms in his/her seat, or just leaves his/her seat in the classroom.
    2. Runs about or climbs excessively in situations where inappropriate.
    3. Cannot play quietly, is always "on the go," or acts as if being driven by something.
    4. Talks excessively and blurts out answers.
    5. Has trouble waiting his turn, interrupts, intrudes on others.
  2. Symptoms of inattention displayed by the child:
    1. Seems to make careless mistakes, or doesn't seem to pay attention to details.
    2. Has trouble sustaining attention, and does not seem to listen when spoken to directly.
    3. Fails to finish tasks, and has trouble organizing tasks and activities.
    4. Avoids tasks requiring sustained mental effort, and often loses things necessary for a task or activity (never remembers to bring a pencil to class or leaves his homework at school every day).
    5. Easily distracted by extraneous stimuli, and forgetful in daily activities.

To be diagnosed as ADHD-H, the child must display six or more symptoms of hyperactivity/impulsivity but less than six symptoms of inattention. Again, these must be observed in at least two settings and have lasted for more than six months. More males than females are diagnosed with this condition.

To be diagnosed with ADHD-I, there must be evidence of six or more symptoms of inattention, but less than six symptoms of hyperactivity/impulsivity that have been clearly observed in the two settings and have been present for six months or more. More females than males are diagnosed with this subtype. This diagnosis can be more easily missed because the child usually doesn't cause trouble for anyone (except, perhaps, the mother, who wonders why on earth the child can't remember to put her socks on in the morning). ADHD-I is more likely to be overlooked or diagnosed much later than the other types.

In the combined subtype, ADHD-C, there must be six or more symptoms of inattention and six or more symptoms of hyperactivity/impulsivity present with the symptoms observed in at least two settings and having the requisite duration of six months or more. This is the most common subtype, and the behavior of the child is more likely to cause peer rejection. It is the most common and most frustrating form, because it is the most resistant to treatment. Most children with ADHD-C engage in acts that are considered socially objectionable. Their excesses in behavior result from a combination of high social interest, explosive temperaments, and an impulsive style. They are often out of sync with the events around them.

ADHD can be inherited and the chances range from 25 to 31% if one parent has ADHD. The chances increase if both parents are affected. Even if a parent has never been diagnosed with ADHD, the child has a greater chance of having the disorder if an aunt or uncle have ADHD.

About 3 to 5% of school-age children in this country have been diagnosed with ADHD, and there are no striking cultural or ethnic differences. It is usually first diagnosed in the elementary school years and is difficult, if not impossible, to diagnose in children under 4 or 5. In fact, Dr. Antshel stated his belief that to diagnose a child any earlier would be very wrong. Almost any two year old, for instance, has behaviors that would be consistent with ADHD. These behaviors are normal for that age, and the child will outgrow them in the normal course of events.

There are certain disorders that are associated with ADHD. These include learning disabilities, Oppositional-Defiant Disorder, and mood and anxiety disorders.

Currently there are only two metabolic disorders considered to be definitely associated with ADHD - PKU and the Urea Cycle Disorders. In PKU there is an area of the brain called the hypodopaminergic prefrontal cortex that appears to be compromised. There is also delayed myelination and structural brain damage caused by high blood Phe levels early in life and a "toxic" effect caused by concurrent Phe levels. Myelin is a fat-like substance, the principal component of a sheath that surrounds the nerve fibers in the brain and spinal cord. It protects the nerve fibers and allows for the conduction of nerve impulses. In the Urea Cycle Disorders, the high ammonia levels can give a presentation of ADHD particularly in the partial defects.

MSUD and Homocystinuria are two metabolic orders that are presently considered likely to be associated with ADHD. In MSUD there is also the phenomenon of delayed myelination, and there appears to be nerve cell loss in an area of the brain called the substantia nigra. Homocystinuria presents with decreased myelination, and isolated cell death occurs in a part of the brain called the globus pallidus. Other metabolic disorders are not, at this time, recognized as being associated with ADHD.

If you suspect that your child has ADHD, check with the school and arrange to have a multi-disciplinary evaluation. Treatment may involve therapy (behavioral and/or family), making academic modifications, medication and continued monitoring.

The bottom line is that some metabolic disorders are associated with an increased risk for ADHD and research is ongoing to determine whether there may be more. ADHD is treatable and treatment should be multifaceted. Research continues in new pharmacological and ecological treatments.

Resources are available for understanding and dealing with ADHD. Children and Adults with Attention-deficit/Hyperactivity Disorder (CHADD) is an organization devoted to informing people about the disorder. It can be accessed by mail at 8181 Professional Place, Suite 201, Landover, MD 20785 or on the web at www.chadd.org. An ADHD Consensus Statement is accessible at http://odp.od.nih. gov/consensus/cons/10/110_statement.htm, and The ADHD Report is available from Guilford Publications on their web site: www.guilford.com or call 800-365-7006 or 212-431-9800.

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