Focus
Che cosa deve sapere il pediatra delle malattie rare
WHAT THE PAEDIATRICIANS MUST KNOW ABOUT RARE DISEASES
A. Ventura, A. Gagliardo, I. Berti, F. Marchetti
Maggio 2003 - pagg. 292
Abstract
Rare diseases constitute a highly eterogeneous category of (mainly genetic) disorders.
Even if the individual diseases are rare, due to their global incidence, rare diseases represent
both an important cause of morbidity and mortality and a challenge for the health
care system. Based on a series of exemplary cases, the Authors define the possible role of
general paediatricians in the diagnosis, treatment and care of children with rare diseases,
focusing on six points: 1. the need to be up-to-date on the diagnostic tools (for instance
on the use of FISH in the diagnosis of mental retardation); 2. the need to be up-to-date on
the therapeutic options: with drugs (as in the exemple of the biphosphonates in osteogenesis
imperfecta or in that of the nitrotrifluoromethylbenzoil-NTBC-in thyrosinemia), with
hormones (as in the exemple of growth hormone in Turner syndrome), with surgery (as in
the case of severe genetic craniostenosis), with enzymatic replacement (as in the case of
Gaucher disease type I or Fabry disease ), with bone marrow transplantation (as in the
case of malignant osteopetrosis or in that of selected cases of MPS 1H); 3. the need to
make a correct diagnosis, thus avoiding potentially serious consequences (as in the case
of fructose intolerance); 4. the need for timely start of effective therapy (as in the case of
some inborn errors of metabolism like biotinidase defect with lactic acidosis or in that of
the congenital immunologic defect presenting as autoimmune disorders without infections-
IPEX, Wiskott-Aldrich disease-, or in familiar periodic fevers); 5. the need to give the right
preventive advice (as in the case of maternal phenylketonuria for avoiding mental retardation
and microcephalia in the newborn); 6. the need to assist the family and the child in
any situation, even when there is nothing to do.
Parole chiave
Classificazione MeSH
Biotinidase Deficiency
Bone Marrow Transplantation (23)
Diphosphonates (13)
Enzyme Replacement Therapy (19)
Fabry Disease (10)
Fructose Intolerance (10)
Gaucher Disease (13)
In Situ Hybridization, Fluorescence (4)
Intellectual Disability (66)
Metabolism, Inborn Errors (31)
Mucopolysaccharidosis I (7)
Osteogenesis Imperfecta (5)
Phenylketonurias (11)
Rare Diseases (43)
Turner Syndrome (29)
Tyrosinemias (3)
Wiskott-Aldrich Syndrome (10)
Bibliografia
1. Dionisi-Vici C, Rizzo C, Burlina A, et al. Inborn
errors of metabolism in the Italian pediatric
population: a national retrospective survey.
J Pediatr 2002;140:321-7.
2. Demori E, Gambel Benussi D, Luchesi A, et al. Ibridazione in situ fluorescente e suoi utilizzi diagnostici in citogenetica. Medico e Bambino 2000;19:44-8.
3. Saccone S, De Sario A, Della Valle G, et al. The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosome. Proc Natl Acad Sci USA 1992;89: 4913-7.
4. National Institutes of Health and Institute of Molecular Medicine Collaboration. A complete set of human telomeric probes and their clinical application. Nat Genet 1996;14:86-9.
5. Knight SJ, Regan R, Nicod A, et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 1999; 354:1676-81.
6. De Vries BBA, White SM, Knight SJL, et al. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet 2001;38:145-50.
7. Hecimovic S , Tarnik IP, Bariι I, et al. Screening for fragile X sindrome: results from a school for mentally retarded children. Acta Paediatr 2002;91:535-39.
8. Astrom E, Soderhall S. Beneficial effect of long term intravenous biphosphonate treatment of osteogenesis imperfecta. Arch Dis Child 2002; 86: 356-64.
9. Bembi B, Parma A, Bottega M, et al. Intravenous Pamidronate treatment in osteogenesis imperfecta. J Pediatr 1997;131:622-5.
10. Sas TC, Muinck Keizer-Schrama SM, Duth Advisory Group on Growth Hormone Turners sindrome: a paediatric perspective. Horm Res 2001;56(suppl 1):38-43.
11. Early initiation of growth hormone treatment allows age appropriate estrogen use in Turners sindrome. J Clin Endocrinol Metab 2001;86:1936-41.
12. Savendahl L, Davenport ML. Delayed diagnoses of Turners syndrome: proposed guidelines for change. J Pediatr 2000;137:455-9.
13. Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of Enzyme replacement therapy in 1028 patients with type 1 Gaucher Disease after 2-5 years of treatment: a report from the Gaucher registry. Am J Med 2002;113: 112- 9.
14. Bembi B, Zanatta M, Carrozzi M, et al. Enzyme replacement treatment in type 1 and type 3 Gauchers disease. Lancet 1994; 344: 1679-82.
15. Whitley CB, Belani KG, Chang PN, et al. Long term outcome of Hurler sindrome following bone marrow transplantation. Am J Med Genet 1993;46:209-18.
16. Hite SH, Peters C, Krivit W. Correction of odontoid dysplasia following bone marrow transplantation and engraftment (in Hurler syndrome MPS 1H). Pediatr Radiol 2000; 30(7):464-70.
17. Grewal SS, Krivit W, Defor TE, et al. Outcome of second hematopoietic cell transplantation in Hurler sindrome. Bone Marrow Transplantation 2002;29:491-6.
18. Gerritsen E, Vossen J, Fasth A, et al. Bone Marrow Transplantation for autosomal recessive osteopetrosis. J Pediatr 1994;125:896-902.
19. Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 2002; 359(9303):317-8.
20. Wang WC, Wyn LW, Roger ZR, et al. A two years pilot trial of hydroxyurea in very young children with sickle cells anemia. J Pediatr 2001;139:790-6.
21. Raben N, Plotz P, Byrene BJ. Acid alphaglycosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med 2002;2:145-66.
22. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease tipe II in the Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999;7:713-6.
23. Bennett CL, Ochs HD. IPEX is inique Xlinked sindrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 2001;13:533-8.
24. Pignata C, et al. per il Gruppo di Studio sulla CGD della Societΰ di Immunologia Pediatrica. Malattia Granulomatosa Cronica. Una diagnosi che puς sfuggire. Medico e Bambino 1998;17:155-60.
25. Drenth JPH, Van der Meer JWM. Hereditary Periodic Fever. N Eng J Med 2001;345: 1748-57.
26. Nassimbeni G. Fenilchetonuria materna. Medico e Bambino 1997;16:251-3.
2. Demori E, Gambel Benussi D, Luchesi A, et al. Ibridazione in situ fluorescente e suoi utilizzi diagnostici in citogenetica. Medico e Bambino 2000;19:44-8.
3. Saccone S, De Sario A, Della Valle G, et al. The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosome. Proc Natl Acad Sci USA 1992;89: 4913-7.
4. National Institutes of Health and Institute of Molecular Medicine Collaboration. A complete set of human telomeric probes and their clinical application. Nat Genet 1996;14:86-9.
5. Knight SJ, Regan R, Nicod A, et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 1999; 354:1676-81.
6. De Vries BBA, White SM, Knight SJL, et al. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet 2001;38:145-50.
7. Hecimovic S , Tarnik IP, Bariι I, et al. Screening for fragile X sindrome: results from a school for mentally retarded children. Acta Paediatr 2002;91:535-39.
8. Astrom E, Soderhall S. Beneficial effect of long term intravenous biphosphonate treatment of osteogenesis imperfecta. Arch Dis Child 2002; 86: 356-64.
9. Bembi B, Parma A, Bottega M, et al. Intravenous Pamidronate treatment in osteogenesis imperfecta. J Pediatr 1997;131:622-5.
10. Sas TC, Muinck Keizer-Schrama SM, Duth Advisory Group on Growth Hormone Turners sindrome: a paediatric perspective. Horm Res 2001;56(suppl 1):38-43.
11. Early initiation of growth hormone treatment allows age appropriate estrogen use in Turners sindrome. J Clin Endocrinol Metab 2001;86:1936-41.
12. Savendahl L, Davenport ML. Delayed diagnoses of Turners syndrome: proposed guidelines for change. J Pediatr 2000;137:455-9.
13. Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of Enzyme replacement therapy in 1028 patients with type 1 Gaucher Disease after 2-5 years of treatment: a report from the Gaucher registry. Am J Med 2002;113: 112- 9.
14. Bembi B, Zanatta M, Carrozzi M, et al. Enzyme replacement treatment in type 1 and type 3 Gauchers disease. Lancet 1994; 344: 1679-82.
15. Whitley CB, Belani KG, Chang PN, et al. Long term outcome of Hurler sindrome following bone marrow transplantation. Am J Med Genet 1993;46:209-18.
16. Hite SH, Peters C, Krivit W. Correction of odontoid dysplasia following bone marrow transplantation and engraftment (in Hurler syndrome MPS 1H). Pediatr Radiol 2000; 30(7):464-70.
17. Grewal SS, Krivit W, Defor TE, et al. Outcome of second hematopoietic cell transplantation in Hurler sindrome. Bone Marrow Transplantation 2002;29:491-6.
18. Gerritsen E, Vossen J, Fasth A, et al. Bone Marrow Transplantation for autosomal recessive osteopetrosis. J Pediatr 1994;125:896-902.
19. Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 2002; 359(9303):317-8.
20. Wang WC, Wyn LW, Roger ZR, et al. A two years pilot trial of hydroxyurea in very young children with sickle cells anemia. J Pediatr 2001;139:790-6.
21. Raben N, Plotz P, Byrene BJ. Acid alphaglycosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med 2002;2:145-66.
22. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease tipe II in the Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999;7:713-6.
23. Bennett CL, Ochs HD. IPEX is inique Xlinked sindrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 2001;13:533-8.
24. Pignata C, et al. per il Gruppo di Studio sulla CGD della Societΰ di Immunologia Pediatrica. Malattia Granulomatosa Cronica. Una diagnosi che puς sfuggire. Medico e Bambino 1998;17:155-60.
25. Drenth JPH, Van der Meer JWM. Hereditary Periodic Fever. N Eng J Med 2001;345: 1748-57.
26. Nassimbeni G. Fenilchetonuria materna. Medico e Bambino 1997;16:251-3.