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The last day of the past is the first day of the future: Transitional care for genetic patients

  • Charles R. Scriver
    Correspondence
    Requests for reprints should be addressed to Charles R. Scriver, MDCM, Department of Human Genetics, McGill University, and Montreal Children's Hospital Research Institute, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada
    Affiliations
    Department of Human Genetics, McGill University (CRS), and Montreal Children's Hospital Research Institute (CRS), Montreal, Quebec, Canada
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  • Philip J. Lee
    Affiliations
    Charles Dent Metabolic Unit, The National Hospital for Neurology and Neurosurgery (PJL), Queen Square, London, United Kingdom
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      Wordsworth said: “The child is father to the man,” to which we would add “and the child is mother to the woman.” Children grow up and carry their biological identity into adult life, which is why an anonymous journalist, writing in The Economist (June 14, 2003), warned us that there are fetal (and childhood) origins of adult-onset disease—“the child is father to the patient.
      Wordsworth further opined that “we come trailing clouds of glory.” The glory includes biologic variation in maladaptive forms, a substantial fraction of which is expressed in utero, during infancy, and in childhood. These results are the many manifestations of genetic disease that remain with the person into and through adulthood. The range and complexities of those mutant gene products, the proteins, and thus a potential range of new drug targets were elegantly summarized in the issue of Nature dedicated to the Human Genome Project (
      • Jimenez-Sanchez G.
      • Childs B.
      • Valle D.
      Human disease genes.
      ). Success in past encounters with genetic disease, both scientific and medical, is now having an effect on the practice of family medicine, internal medicine, obstetrics, and other specialties. A new medical demography is emerging, and with it the question “Can we ease the transition out of health care systems for youth into health care for those adult-age patients who bring with them their genetic diseases?”
      Is it an important problem? Yes it is. The established prevalence of genetic disease in the population, whether it be chromosomal, Mendelian, or multifactorial, is not trivial (
      • Baird P.A.
      • Anderson T.W.
      • Newcombe H.B.
      • Lowry R.B.
      Genetic disorders in children and young adults: a population study.
      ). One in 20 residents in populations such as those in North America will have a fully expressed variant (genetic) phenotype at age 25 years. During their lifetimes, 60% of residents will experience a disease with a major biologic (genetic) component of cause. The latter are those patients whose disease propensity was laid down in the periods of fetal and infantile life; they have oligogenic complex disease traits. Many other genetic problems belong in the category of orphan diseases; they run into the hundreds, even thousands (

      McKusick VA. Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders. Available at: http://www.ncbi.nlm.nih.gov/entrez/.

      ). Among the inborn errors of metabolism, each a typical orphan disease, there will be patients who need lifelong treatment (e.g., phenylketonuria), others whose disease process will involve gradual deterioration (e.g., lysosomal storage diseases), others with early-onset and permanent harm in the absence of effective tretment (e.g., the Lesch-Nyhan disorder), and those whose early years are benign yet will be followed by progressive clinical deterioration (e.g., the leukodystrophies). Each patient and disease calls for a compassionate, informed, coherent, and continuing response from the providers of health care (
      ).
      In this issue of the Journal, Hanley describes a harbinger of the changing medical demographic (
      • Hanley W.B.
      Adult phenylketonuria.
      ). Pediatric patients with successfully treated phenylketonuria become independent adults, yet their needs for both knowledgeable and compassionate care continue. Phenylketonuria, a Mendelian phenotype causing mental retardation in the untreated state, was the first recognized genetic disease to respond to a systematic treatment (
      • Scriver C.R.
      • Kaufman S.
      Hyperphenylalaninemia: phenylalanine hydroxylase deficiency.
      ,

      Donlon J, Levy H, Scriver CR. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Sly SW, et al, eds. The Metabolic and Molecular Bases of Inherited Disease [online version]. New York, New York: McGraw-Hill; 2004. Available at:http://genetics.accessmedicine.com/.

      ). Successful treatment (by restrictive diet) of this otherwise devastating genetic disease changed our view of genetic disease in general—genetic destiny could be modified. The last half century of genetics in medicine is testimony to that paradigm shift.
      Because phenylketonuria is treatable but requires early diagnosis, it became the model a generation ago for population-based newborn screening programs. Those programs have since been expanding to include many other treatable diseases. By age 20 years, there are more than 8000 patients with hyperphenylalaninemia alone in the U.S. population, and twice as many in Europe. Indeed, the number with other hereditary metabolic diseases is considerably greater. Moreover, among the other genetic diseases that affect the 1 in 20 persons by age 25 years, there are persons with Down syndrome, for example, whose integration into society today is quite different from that in the not-so-distant past. It is no surprise then that an adolescent patient with yet another genetic disorder—cystic fibrosis—has a parent and an attending pediatrician who published creative suggestions for transitional care in what they call the “Medical Home Model” (
      • Olsen D.
      • Swigonski N.L.
      Transition to adulthood: the important role of the pediatrician.
      ).
      Is transitional care in place? Are health care providers ready? In the case of phenylketonuria, the prototype here, the challenge was anticipated at least a decade ago (
      Medical Research Council (UK)
      Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story.
      ,
      • Lee P.J.
      Growing older: the adult metabolic clinic.
      ) but still is not well met. Someone is needed to supervise continuing treatment, in the absence of which neuropsychometric and neurologic dysfunction are likely to emerge. Furthermore, family physicians and obstetricians must know how to prevent the devastating effects of maternal hyperphenylalaninemia on the developing fetus (
      • Koch R.
      • De La Cruz F.
      • Azen C.G.
      The Maternal Phenylketonuria Collaborative Study: new developments and the need for new strategies.
      ). Physicians involved with the care of maternal diabetes already know something about the disturbing effects of abnormal maternal metabolism on the fetus. Here is evidence of both the complexity and the importance of transitional care for patients with genetic disease.
      For persons with hereditary metabolic disorders, there are many particular obstacles to overcome. The dietary and pharmacologic management may be complex, and patients are concerned that sufficient expertise in adult internal medicine may not exist. The pediatrician may be overprotective out of concern for the long-term outcome. Parents of the patients may be unwilling to allow their child more independence or to relinquish the pediatric services that supervised their child-patient, being uncertain of the services that lie ahead. Will expert care continue? Will someone be there to listen and to monitor treatment? A document assembled jointly by U.S. professional societies representing pediatrics, family medicine, and internal medicine (
      American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians, American Society of Internal Medicine
      A consensus statement on health care transitions for young adults with special health care needs.
      ) highlights the approaches required to maximize lifelong care of patients with special needs.
      How can we help the internist, the primary care physicians, and others who will be involved? A look at other specialties may reveal helpful models. Increasing numbers of children with malignancies are surviving into adulthood; their care and surveillance continues. In Germany, for instance, vertical networks have been successfully established among hospitals, cancer registries, and general practitioners to provide the transfer of information and the standardization of care throughout the country (

      Calaminus G. Vertical networks in paediatric oncology: transfer information from specialized paediatric cancer services to general medical care (adult institutions included). In: Inborn Errors of Metabolism–Pathways into Adulthood. Symposia Proceedings. Heilbron, Germany: SPS Publications; 2004:45–50.

      ). Rheumatologists have patients whose disease begins in childhood yet continues into adulthood. Over one third of young people with juvenile idiopathic arthritis continue to have active disease as adults (
      • Foster H.E.
      • Marshall N.
      • Myers A
      • et al.
      Outcome in adults with juvenile idiopathic arthritis.
      ); transitional care provides the multidisciplinary expertise required for these patients (
      • Shaw K.L.
      • Southwood T.R.
      • McDonagh J.E.
      Improving the quality of life for adolescents with juvenile idiopathic arthritis: results of a postal survey.
      ).
      Should there be a genetic subspecialty for adult patients? The simple answer is “yes.” For comparison, pediatric oncology and rheumatology, as well as other children's specialties such as cardiology, gastroenterology, and nephrology, benefit from having adult specialists with whom to interact. Metabolic medicine and biochemical genetics have not been so fortunate. Nonetheless, in Europe and the United Kingdom, progress is being made, albeit slowly, to establish a specialty in metabolic medicine within chemical pathology and general internal medicine, with recognized programs for the training of specialists (
      • Lee P.J.
      Growing older: the adult metabolic clinic.
      ).
      Meanwhile, beyond the diagnostic phenotype, whatever its name may be, there is the patient. As always, our first responsibility as physicians is to that person; we serve the patient. If we cannot provide continuing care, the transition of patients with genetic disease into adult-age medical care will have been bought at a Faustian bargain: an uncertain future will have been traded for a successful past. These thoughts are likely to be on the mind of every young transitional patient whose last day of the past is the first of her or his future in medical care.

      Acknowledgment

      Philip Lee acknowledges the late Professor Charles Dent and Dr. David Brenton for having the foresight to establish and maintain the clinic dedicated to adults with inborn errors of metabolism in London. The authors thank Teresa Rudkin, MD, advocate for the primary care physician, and Serge Melançon, MD, for reading the manuscript.

      References

        • Jimenez-Sanchez G.
        • Childs B.
        • Valle D.
        Human disease genes.
        Nature. 2001; 409: 853-855
        • Baird P.A.
        • Anderson T.W.
        • Newcombe H.B.
        • Lowry R.B.
        Genetic disorders in children and young adults: a population study.
        Am J Hum Genet. 1988; 42: 677-693
      1. McKusick VA. Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders. Available at: http://www.ncbi.nlm.nih.gov/entrez/.

      2. Burgard P. Lee P.J. Wendel E. Inborn Errors of Metabolism–Pathways into Adulthood Symposia Proceedings. SPS Publications, Heilbron, Germany2004: 1-89
        • Hanley W.B.
        Adult phenylketonuria.
        Am J Med. 2004; 117: 590-595
        • Scriver C.R.
        • Kaufman S.
        Hyperphenylalaninemia: phenylalanine hydroxylase deficiency.
        in: Scriver C.R. Beaudet A. Sly W.S The Metabolic and Molecular Bases of Inherited Disease. McGraw Hill, New York, New York2001: 1667-1724
      3. Donlon J, Levy H, Scriver CR. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Sly SW, et al, eds. The Metabolic and Molecular Bases of Inherited Disease [online version]. New York, New York: McGraw-Hill; 2004. Available at:http://genetics.accessmedicine.com/.

        • Olsen D.
        • Swigonski N.L.
        Transition to adulthood: the important role of the pediatrician.
        Pediatrics. 2004; 113: 159-162
        • Medical Research Council (UK)
        Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story.
        BMJ. 1993; 306: 115-119
        • Lee P.J.
        Growing older: the adult metabolic clinic.
        J Inherit Metab Dis. 2002; 25: 252-260
        • Koch R.
        • De La Cruz F.
        • Azen C.G.
        The Maternal Phenylketonuria Collaborative Study: new developments and the need for new strategies.
        Pediatrics. 2003; 112: 1513-1587
        • American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians, American Society of Internal Medicine
        A consensus statement on health care transitions for young adults with special health care needs.
        Pediatrics. 2002; 110: 1304-1306
      4. Calaminus G. Vertical networks in paediatric oncology: transfer information from specialized paediatric cancer services to general medical care (adult institutions included). In: Inborn Errors of Metabolism–Pathways into Adulthood. Symposia Proceedings. Heilbron, Germany: SPS Publications; 2004:45–50.

        • Foster H.E.
        • Marshall N.
        • Myers A
        • et al.
        Outcome in adults with juvenile idiopathic arthritis.
        Arthritis Rheum. 2003; 48: 767-775
        • Shaw K.L.
        • Southwood T.R.
        • McDonagh J.E.
        Improving the quality of life for adolescents with juvenile idiopathic arthritis: results of a postal survey.
        Rheumatology. 2004; 43: 211-219