TY  - CHAP
M1  - Book, Section
TI  - Clinical Phenotypes: Diagnosis/Algorithms
A1  - Saudubray, Jean-Marie
A1  - Charpentier, Christiane
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Despite  the  abundance  of  new  case  reports,  there  is  considerable  evidence  that  many  inherited  metabolic  disorders  remain  undiagnosed  or  misdiagnosed.  There  are  a  number  of  reasons,  the  most  important  of  which  is  the  fact  that  many  physicians  are  not  aware  of  most  of  the  highly  specific  symptoms  or  syndromes  that  are  excellent  keys  to  the  diagnosis  and  consequently  do  not  perform  comprehensive  examinations.From  a  clinical  point  of  view,  all  the  inborn  errors  of  metabolism  can  be  divided  into  two  large  categories:  Category  1.  Diseases  that  involve  only  one  functional  system  or  affect  only  one  organ  or  anatomic  system.  Presenting  symptoms  are  uniform,  and  diagnosis  is  usually  easy  even  when  the  basic  biochemical  lesion  gives  rise  to  systemic  consequences.  Category  2.  Diseases  in  which  the  basic  biochemical  lesion  either  affects  a  metabolic  pathway  common  to  a  large  number  of  cells  or  organs  or  is  restricted  to  one  organ  but  gives  rise  to  humoral  and  systemic  consequences.  Presenting  symptoms  are  very  diverse.  The  central  nervous  system  is  frequently  involved  in  advanced  disease,  and  diagnosis  may  be  rendered  difficult  by  the  presence  of  secondary  abnormalities.  This  category  includes  most  inborn  errors  of  intermediary  metabolism,  diseases  of  intracellular  trafficking,  and  lysosomal  disorders.The  second  category  can  be  subdivided  on  the  basis  of  pathophysiology  into  three  groups  that  are  useful  for  diagnosis.  Group  1.  Diseases  that  disturb  the  synthesis  or  catabolism  of  complex  molecules  (lysosomal  and  peroxisomal  disorders;  disturbances  of  intracellular  trafficking  and  secretory  protein  processing).  Clinical  symptoms  are  permanent,  progressive,  independent  of  intercurrent  events,  and  unrelated  to  food  intake.  Group  2.  Inborn  errors  of  intermediary  metabolism  that  lead  to  acute  or  progressive  intoxication  caused  by  accumulation  of  toxic  compounds  proximal  to  the  metabolic  block.  The  group  includes  aminoacidopathies,  most  organic  acidurias,  congenital  urea  cycle  defects,  and  sugar  intolerances.  In  these  conditions,  a  symptom-free  interval  is  followed  by  clinical  signs  of  acute  or  chronic  intoxication  and  by  recurrent  metabolic  disturbances.  Clinical  expression  is  often  late  in  onset  and  intermittent.  Diagnosis  is  easy,  relying  mainly  on  chromatography  of  plasma  and  urine  amino  acids  or  organic  acids.  Treatment  involves  removing  the  toxin.  Group  3.  “Energy  deficiency”  disorders,  in  which  symptoms  are  caused  at  least  partly  by  a  deficiency  in  energy  production  or  utilization  resulting  from  an  inborn  error  of  intermediary  metabolism  in  liver,  myocardium,  muscle,  or  brain.  This  group  includes  glycogenosis,  gluconeogenesis  defects,  congenital  lactic  acidemias,  fatty  acid  oxidation  defects,  and  mitochondrial  respiratory  chain  disorders.  These  diseases  present  an  overlapping  clinical  spectrum,  and  manifestations  sometimes  result  from  accumulation  of  toxic  compounds  as  well  as  from  the  deficiency  in  energy  production.  Common  symptoms  include  hypoglycemia,  hyperlactacidemia,  severe  generalized  hypotonia,  myopathy,  cardiomyopathy,  failure  to  thrive,  cardiac  failure,  circulatory  collapse,  sudden  infant  death  syndrome,  and  congenital  malformations,  the  last  suggesting  that  the  abnormal  process  affected  fetal  energy  pathways.The  clinical  diagnostic  circumstances  observed  in  inborn  errors  of  metabolism  are  divided  in  this  chapter  into  eight  categories:  presentation  in  the  neonatal  period,  intermittent  late-onset  acute  presentation,  progressive  neurologic  symptoms,  ocular  symptoms,  skin  symptoms,  hematologic  symptoms,  visceral  symptoms  or  syndromes,  and  endocrine  symptoms.  The  following  outline  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/23
UR  - ommbid.mhmedical.com/content.aspx?aid=1181419729
ER  -