Inborn Errors of Metabolism

AIIMS- NICU protocols 2010
Approach to Inborn Errors of Metabolism Presenting in the Neonate

Suvasini Sharma, Pradeep Kumar, Ramesh Agarwal, Madhulika Kabra,
Ashok Deorari, Vinod Paul
Department of Pediatrics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi 11002
Address for correspondence
Dr Ashok K Deorari
Professor
Department of Pediatrics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi 11002
!mail" asho#deorari$%&'hotmail(com
Downloaded from www.newbornwhocc.org
Abstract
In)orn errors of meta)olism *I!M+ are an important cause of acute illness in new)orns(
Presentation ma, mimic common neonatal conditions such as sepsis( Prompt detection
re-uires a high inde. of suspicion and the earl, measurement of )iochemical mar#ers
such as )lood ammonia( Diagnosis is important not onl, for treatment )ut also for genetic
counselling( /uidelines for diagnosis and earl, management of I!M presenting in the
neonatal period are descri)ed(
Key words: In)orn errors of meta)olism, encephalopath,, h,perammonemia
In)orn errors of meta)olism *I!M+ are disorders in which there is a )loc# at some point
in the normal meta)olic pathwa, caused ), a genetic defect of a specific en0,me( 1he
num)er of diseases in humans #nown to )e attri)uta)le to inherited point defects in
meta)olism now e.ceeds %00(
1
2hile the diseases indi3iduall, are rare, the, collecti3el,
account for a significant proportion of neonatal and childhood mor)idit, and mortalit,(
Diagnosis is important not onl, for treatment and prognostication )ut also for genetic
counselling and antenatal diagnosis in su)se-uent pregnancies(
Clinical Presentation:
Se3ere illness in the new)orn, regardless of the underl,ing cause, tends to manifest with
non4specific findings, such as poor feeding, drowsiness, letharg,, h,potonia and failure
to thri3e( I!M should )e considered in the differential diagnosis of an, sic# neonate
along with common ac-uired causes such as sepsis, h,po.ic4ischemic encephalopath,,
duct4dependant cardiac lesions, congenital adrenal h,perplasia and congenital infections(
5linical pointers towards an underl,ing I!M include
2
"
Deterioration after a period of apparent normalc,
Parental consanguinit,
6amil, histor, of une.plained neonatal deaths
7apidl, progressi3e encephalopath, and sei0ures of une.plained cause
Se3ere meta)olic acidosis
Persistent 3omiting
Peculiar odor *urine, cerumen+
Acute fatt, li3er or 8!99P *hemol,sis, ele3ated li3er en0,mes : low platelet
counts+ during pregnanc," seen in women carr,ing fetuses with long4chain4;4
h,dro.,ac,l4coen0,me deh,drogenase deficienc, *958ADD+(
1a)le 1 descri)es e.amination findings that ma, pro3ide a clue to the underl,ing I!M(
Patterns of presentation include
2,;
"
1) ncephalopath! w"th or w"tho#t metabol"c ac"dos"s$ encephalopath,, sei0ures,
and tone a)normalities are predominant presenting features of organic acidemias,
urea c,cle defects and congenital lactic acidosis( Isolated intracta)le sei0ures are
prominent in p,rido.ine dependenc,, p,rido.al phopspahte dependenc,, folinic4
acid responsi3e sei0ures, and glucose transporter 1 defecienc,(
<
2) Ac#te l"%er d"sease$ 1his could manifest as4
=aundice alone4 /il)ert s,ndrome, 5riggler4Na>>ar s,ndrome
8epatic failure *>aundice, ascites, h,pogl,cemia, coagulopath,+4
1,rosinemia, galactosemia, neonatal hemochromatosis, gl,cogen storage
disease t,pe I?(
Neonatal cholestasis" alpha41 antitr,psin deficienc,, Niemann4Pic#
disease t,pe 5(
8,pogl,cemia" persistent and se3ere h,pogl,cemia ma, )e an indicator of
an underl,ing I!M( 8,pogl,cemia is a feature of galactosemia, fatt, acid
o.idation defects, organic acidemias, gl,cogen storage disorders and
disorders of gluconeogenesis(
3) D!smorph"c feat#res$ seen in pero.isomal disorders, p,ru3ate deh,drogenase
deficienc,, congenital disorders of gl,cos,lation *5D/+, and l,sosomal storage
diseases( Some I!Ms ma, present with non4immune h,drops fetalis@ these include
l,sosomal storage disorders and 5D/(
4) Card"ac d"sease$ cardiom,opath, is a prominent feature in some I!M including
fatt, acid o.idation defects, gl,cogen storage disease t,pe II and mitochondrial
electron transport chain defects(
Inestigations
Meta)olic in3estigations should )e initiated as soon as the possi)ilit, is considered( 1he
outcome of treatment of man, I!M especiall, those associated with h,perammonemia is
directl, related to the rapidit, with which pro)lems are detected and appropriate
management instituted(
!irst line inestigations "metabolic screen#:
1he following tests should )e o)tained in A99 )a)ies with suspected I!M(
1+ 5omplete )lood count" *neutropenia and throm)oc,topenia seen in propionic and
meth,lmalonic academia+
2+ Arterial )lood gases and electrol,tes
;+ Alood glucose
4) Plasma ammonia *Normal 3alues in new)orn" 041%0 gBdl or &<410C molB9+
%+ Arterial )lood lactate *Normal 3alues" 0(%41(& mmolB9+
&+ 9i3er function tests
C+ Drine #etones
E+ Drine reducing su)stances(
+ Serum uric acid *low in mol,)denum cofactor deficienc,+(
6igure 1 gi3es the algorithmic approach to a new)orn with suspected I!M( Disease
categor, can )e diagnosed )ased on )lood ammonia, )lood gas anal,sis and urine #etone
testing( 8,perammonemia without acidosis is caused ), urea c,cle defects( Meta)olic
acidosis with or without h,perammonemia is a feature of organic acidemias and fatt,
acid o.idation defects( 6igure 2 e.plains the algorithmic approach to neonate with
persistent h,pogl,cemia and suspected underl,ing I!M( 1a)le 2 e.plains the
categori0ation of I!M )ased on simple meta)olic screening tests(
$econd line inestigations "ancillary and confirmatory tests#
1hese tests need to )e performed in a targeted manner, )ased on presumpti3e diagnosis
reached after first line in3estigations"
1+ /as chromatograph, mass spectrometr, */5MS+ of urine4 for diagnosis of
organic acidemias(
2+ Plasma amino acids and ac,l carnitine profile" ), tandem mass spectrometr,
*1MS+4 for diagnosis of organic acidemias, urea c,cle defects, aminoacidopathies
and fatt, acid o.idation defects(
;+ 8igh performance li-uid chromatograph, *8P95+" for -uantitati3e anal,sis of
amino acids in )lood and urine@ re-uired for diagnosis of organic acidemias and
aminoacidopathies(
<+ 9actateBp,ru3ate ratio4 in cases with ele3ated lactate(
%+ Drinar, orotic acid4 in cases with h,perammonemia for classification of urea
c,cle defect(
&+ !n0,me assa," 1his is re-uired for definiti3e diagnosis, )ut not a3aila)le for most
I!MFs( A3aila)le en0,me assa,s include" )iotinidase assa,4 in cases with
suspected )iotinidase deficienc, *intracta)le sei0ures, se)orrheic rash, alopecia+@
and ( /A91 *galactose 14phosphate urid,l transferase+ assa,4 in cases with
suspected galactosemia *h,pogl,cemia, cataracts, reducing sugars in urine+(
7) Neuroimaging" M7I ma, pro3ide helpful pointers towards etiolog, while results
of definiti3e in3estigations are pending( Some I!M ma, )e associated with
structural malformations e(g( Gellweger s,ndrome has diffuse cortical migration
and sulcation a)normalities( Agenesis of corpus callosum has )een reported in
Men#eFs disease, p,ru3ate decar)o.,lase deficienc, and non#etotic
h,pergl,cinemia(
%
!.amples of other neuroimaging findings in I!M include"
Maple s,rup urine disease *MSDD+" )rainstem and cere)ellar edema
Propionic : meth,lmalonic acidemia" )asal ganglia signal change
/lutaric aciduria" frontotemporal atroph,, su)dural hematomas
E+ Magnetic resonance spectroscop, *M7S+" ma, )e helpful in selected disorders
!(g( lactate pea# ele3ated in mitochondrial disorders, leucine pea# ele3ated in
MSDD(
9) Drine for alpha4aminoadipic semialdeh,de, 4 ele3ated in p,rido.ine dependent
sei0ures( *test not a3aila)le in India ,et+(
<
10)!lectroencephalograph, *!!/+" some !!/ a)normalities ma, )e suggesti3e of
particular I!M@ e(g( com)4li#e rh,thm in MSDD, )urst suppression in NH8 and
holocar)o.,lase s,nthetase deficienc,(
&
11+ Plasma 3er, long chain fatt, acid *?956A+ le3els" ele3ated in pero.isomal
disorders(
12+ Mutation anal,sis when a3aila)le(
1;+ 5S6 aminoacid anal,sis" 5S6 /l,cine le3els ele3ated in NH8(
Preca%tions to be obsered while collecting samples
1( Should )e collected )efore specific treatment is started or feeds are stopped, as
ma, )e falsel, normal if the child is off feeds(
2. Samples for )lood ammonia and lactate should )e transported in ice and
immediatel, tested( 9actate sample should )e arterial and should )e collected
after 2 hrs fasting in a preheparini0ed s,ringe( Ammonia sample is to )e collected
appro.imatel, after 2 hours of fasting in !D1A 3acutainer( A3oid air mi.ing(
Sample should )e free flowing(
;( Detailed histor, including drug details should )e pro3ided to the la)( *sodium
3alproate therap, ma, increase ammonia le3els+(
$amples to be obtained in infant with s%spected IEM when diagnosis is %ncertain
and death seems ineitable "Metabolic a%topsy#
&'(
1. Alood" %410 ml@ fro0en at 420
0
5@ )oth heparini0ed *for chromosomal
studies+ and !D1A *for DNA studies+ samples to )e ta#en
2. Drine" fro0en at 20
o
5
3. 5S6" store at 20
o
5
4. S#in )iops," ; I 2 mm full thic#ness in culture medium or saline with
glucose( Store at <4E
0
5( Do not free0e(
5. 9i3er and muscle )iops," for histopatholog,, electron microscop,, and
en0,me studie(
6. Hidne, and heart )iops," as indicated(
C( 5linical photograph *in cases with d,smorphism+
E( Infantogram *in cases with s#eletal a)normalities+
)reatment
In most cases, treatment needs to )e instituted empiricall, without a specific diagnosis(
1he meta)olic screen helps to )roadl, categori0e the patientFs I!M *e(g( urea c,cle
defect, organic academia, congenital lactic acidosis etc+, on the )asis of which, empirical
treatment can )e instituted(

Aims of treatment
1( 1o reduce the formation of to.ic meta)olites ), decreasing su)strate a3aila)ilit,
*), stopping feeds and pre3enting endogenous cata)olism+
2( 1o pro3ide ade-uate calories
;( 1o enhance the e.cretion of to.ic meta)olites(
<( 1o institute co4factor therap, for specific disease and also empiricall, if diagnosis
not esta)lished(
%( Supporti3e care4 treatment of sei0ures *a3oid sodium 3alproate ma, increase
ammonia le3els+, maintain eugl,cemia and normothermia, fluid, electrol,te :
acid4)ase )alance, treatment of infection, mechanical 3entilation if re-uired(
Management of hyperammonemia
*' +,
1) Discontinue all feeds( Pro3ide ade-uate calories ), intra3enous glucose and
lipids( Maintain glucose infusion rate E410 mgB#gBmin( Start intra3enous lipid 0(%
gB#gBda, *up to ;gB#gBda,+( After sta)ili0ation graduall, add protein 0(2% gB#g till
1(% gB#gBda,(
2+ Dial,sis is the onl, means for rapid remo3al of ammonia, and hemodial,sis is
more effecti3e and faster than peritoneal dial,sis, howe3er peritoneal dial,sis ma,
)e more widel, a3aila)le and feasi)le( !.change transfusion is not useful(
;+ Alternati3e pathwa,s for nitrogen e.cretion4"
Sodium )en0oate *I? or oral+4 loading dose 2%0 mgB#g then 2%04<00 mgB#gBda,
in < di3ided doses( *Intra3enous preparation not a3aila)le in India+(
Sodium phen,l)ut,rate *not a3aila)le in India+4loading dose 2%0 mgB#g followed
), 2%04%00 mgB#gBda,(
94arginine *oral or I?+4 ;00 mgB#gBda, *Intra3enous preparation not a3aila)le in
India+
94carnitine *oral or I?+4 200 mgB#gBda,
<+ Supporti3e care" treatment of sepsis, sei0ures, 3entilation( A3oid sodium
3alproate(
Ac%te management of newborn with s%spected organic acidemia
++
1+ 1he patient is #ept nil per orall, and intra3enous glucose is pro3ided(
2+ Supporti3e care" h,dration, treatment of sepsis, sei0ures, 3entilation(
;+ 5arnitine" 100 mgB#gBda, I? or oral(
<+ 1reat acidosis" Sodium )icar)onate 0(;%40(%m!-B#gBhr *ma. 142m!-B#gBhr+
%+ Start Aiotin 10 mgBda, orall,(
&+ Start ?itamin A12 142 mgBda, IBM *useful in A12 responsi3e forms of
meth,lmalonic acidemias+
7) Start 1hiamine ;00 mgBda, *useful in thiamine4responsi3e 3ariants of MSDD+(
E+ If h,perammonemia is present, treat as e.plained a)o3e(
Management of congenital lactic acidosis
1+ Supporti3e care" h,dration, treatment of sepsis, sei0ures, 3entilation( A3oid
sodium 3alproate(
2+ 1reat acidosis" sodium )icar)onate 0(;%40(%m!-B#gBhr *ma. 142m!-B#gBhr+
;+ 1hiamine" up to ;00 mgBda, in < di3ided doses(
<+ 7i)ofla3in" 100 mgBda, in < di3ided doses(
%+ Add co4en0,me J" %41% mgB#gBda,
&+ 94carnitine" %04100 mgB#g orall,(
7) Aiotin 10 mgBda,( *Aiotin responsi3e Multiple car)o.,lase deficienc, ma,
present with une.plained lactic acidosis+
12
)reatment of newborn with refractory sei-%res with no obio%s etiology "s%spected
metabolic etiology#
.' +/
1+ If patient persists to ha3e sei0ures despite 2 or ; antiepileptic drugs in ade-uate
doses, consider trial of p,rido.ine 100 mg intra3enousl,( If intra3enous
preparation not a3aila)le, oral p,rido.ine can )e gi3en *1% mgB#gBda,+(
2) If sei0ures persist despite p,rido.ine, gi3e trial of )iotin 10 mgBda, and folinic
acid %mg twice dail, *folinic acid responsi3e sei0ures+( 1rial of p,rido.al
phosphate 10 mgB#gBdose I 2 doses is also recommended, howe3er this is not
a3aila)le in India(
3) 7ule out glucose transporter defect" measure 5S6 and )lood glucose( In glucose
transporter defect, 5S6 glucose le3el is e-ual to or less than 1B;
rd
of the )lood
glucose le3el( 1his disorder responds to the #etogenic diet(
Management of asymptomatic newborn with a history of sibling death with
s%spected IEM:
1+ After )aseline meta)olic screen, start oral de.trose feeds *10K de.trose+(
2+ After 2< hours, repeat screen( If normal, start )reast feeds( Monitor sugar, )lood
gases and urine #etones, )lood ammonia & hourl,(
3) Some authorities recommend starting medium chain trigl,cerides *M51 oil+
)efore starting )reast feeds,
;
howe3er, this is not )eing followed in our center
*)ecause of unpalati)ilit, of M51 oil+(
<+ After <E hours, repeat meta)olic screen( L)tain samples for 1MS and urine
organic acid tests(
%+ 1he infant will need careful o)ser3ation and follow4up for the first few months, as
I!M ma, present in different age groups in mem)ers of the same famil,(
0ong term treatment of IEM
1he following modalities are a3aila)le"
1& D"etar! treatment$ 1his is the mainsta, of treatment in phen,l#etonuria, maple s,rup
urine disease, homoc,stinuria, galactosemia, and gl,cogen storage disease 1,pe I : III(
Special diets for PHD and MSDD are commerciall, a3aila)le in the west( 1hese are not
a3aila)le in India, )ut can )e imported( 1hese special diets are howe3er 3er, e.pensi3e,
and cannot )e afforded ), most Indian patients( Aased on the amino acid content of some
common food products a3aila)le in India, dietar, e.changes are calculated and a low
phen,lalanine diet for PHD and diet low in )ranched chain amino acids for MSDD are
)eing used in our center( 8owe3er, there are no studies to document the efficac, of these
indigenous diets( Some disorders li#e urea c,cle disorders and organic acidurias re-uire
dietar, modification *protein restriction+ in addition to other modalities(
1
1he #etogenic
diet is the treatment of choice for glucose transporter 1 defienc, and p,ru3ate
deh,drogenase deficienc,(
2& n'!me replacement therap! ()*&$ !71 is now commerciall, a3aila)le for some
l,sosomal storage disorders(
1%
8owe3er, these disorders do not manifest in the new)orn
period, an e.ception )eing PompeFs disease */l,cogen storage disorder 1,pe II+ which
ma, present in the new)orn period and for which !71 is now a3aila)le(
+& Cofactor replacement therap!$ 1he catal,tic properties of man, en0,mes depend on
the participation of non protein prosthetic groups, such as 3itamins and minerals, as
o)ligator, cofactors( 1he following co4factors ma, )e )eneficial in certain I!M"
1&
1hiamine" mitochondrial disorders, thiamine responsi3e 3ariants of
MSDD, PD8 deficienc, : comple. I deficienc,+
7i)ofla3in" /lutaric aciduria 1,pe I, 1,pe II, mild 3ariants of !16, !164
D8, comple. I deficienc,
P,rido.ine" %0K of cases of homoc,stinuria due to c,stathionine M4
s,nthetase deficienc,, p,rido.ine dependenc, with sei0ures, .anthurenic
aciduria, primar, h,pero.aluria t,pe I, 8,perornithemia with g,rate
atroph,
5o)alamin" Meth,lmalonic academia *cblA, cbl-&, 8omoc,stinuria and
meth,lmalonic academia *cblC, cblD, cbl.&
6olinic acid" 8ereditar, orotic aciduria, Methionine s,nthase deficienc,,
5ere)ral folate transporter deficienc,, hereditar, folate mala)sorption,
Hearns4Sa,re s,ndrome
Aiotin" Aiotinidase deficienc,, holocar)o.,lase s,nthetase deficienc,
Preention
1) 1enetic co%nselling and prenatal diagnosis" Most of the I!M are single gene
defects, inherited in an autosomal recessi3e manner, with a 2%K recurrence ris#(
1herefore when the diagnosis is #nown and confirmed in the inde. case, prenatal
diagnosis can )e offered, where3er a3aila)le for the su)se-uent pregnancies( 1he
samples re-uired are chorionic 3illus tissue or amniotic fluid( Modalities
a3aila)le are"
1C
Su)strate or meta)olite detection" useful in phen,l#etonuria, pero.isomal
defects(
!n0,me assa," useful in l,sosomal storage disorders li#e Niemann4Pic#
disease, /aucher disease(
DNA )ased *molecular+ diagnosis" Detection of mutation in pro)andB
carrier parents is a prere-uisite(
2) Neonatal screening: 1andem mass spectrometr, is used in some countries for
neonatal screening for I!M( Disorders which can )e detected ), 1MS include
aminoacidopathies * phen,l#etonuria, MSDD, 8omoc,stinuria, 5itrullinemia,
Argininosuccinic aciduria, hepatorenal t,rosinemia+, fatt, acid o.idation defects,
organic acidemias *glutaric aciduria, propionic acidemia, meth,lmalonic
acidemia, iso3aleric acidemia+( 1he appropriate time for collection of samples is
)etween 1 and ; da,s of life( 1he cost of this procedure is high, a potent dis4
in3enti3e for resource poor countries li#e India( Also, the though the test is highl,
sensiti3e, the specificit, is relati3el, low@ and there are difficulties in
interpretation of a)normal test results in apparentl, health, infants(

Concl%sion
I!M collecti3el, represent an important cause of mor)idit, and death in the neonatal
period( 1he most important step in the diagnosis of I!M is clinical suspicion( Screening
in3estigations such as arterial )lood gases, )lood ammonia, lactate, sugar and urine
#etones help to categori0e the possi)le I!M and guide immediate management(
Appropriate immediate treatment not onl, impro3es sur3i3al )ut also reduces the chances
of neurode3elopmental se-uelae(
Do2s and Don2t2s
1+ DonFt thin# of I!M as rare, e.otic and untreata)le disorders(
2) 1hin# of I!M in sic# new)orns in parallel with other common conditions
such as sepsis( 1he signs and s,mptoms are usuall, non specific such as
letharg,, poor feeding and 3omiting(
3) L)ser3e the precautions as e.plained while collecting and storing samples
4) !3en if the chances of sur3i3al appear )lea#, e3er, attempt must )e made
to reach a diagnosis so that parents can )e guided for future pregnanc,(
3eferences
1) 5hilds A, ?alle D, =imene04Sanche0( 1he In)orn error and )iochemical
3aria)ilit,( In" Scri3er 57, Aeaudet A9, Sl, 2S : ?alle D *eds+( 1he meta)olic
and molecular )asis of inherited disease, E
th
ed, New Nor#" Mc/raw48ill, 2001"
1%%41&&(
2) A 5linical guide to inherited meta)olic diseases( =17 5lar#e( ;
rd
!d *200&+,
5am)ridge Dni3ersit, Press, 5am)ridge(
3) 5ataltepe SD, 9e3, 89( In)orn errors of meta)olism( In" 5lohert, =P, !ichenwald
!5, Star# A7 eds( Manual of neonatal care( &
th
!dition( 9ippincott 2illiams :
2il#ins 200E@ Philadelphia" %%E4%C;(
<+ Pearl PS( New treatment paradigms for neonatal meta)olic epilepsises( = Inherit
Meta) Dis 200@ ;2" 20<421;(
%+ Alaser S, 6eigen)aum A( A neuroimaging approach to in)orn errors of
meta)olism( Neuroimag 5lin N Am 200<@ 1<" ;0C4;2(
6) Nordli D7, De ?i3o D5( 5lassification of infantile sei0ures" Implications for
identification and treatment of in)orn errors of meta)olism( = 5hild Neurol 2002@
1C *Suppl ;+" ;S;4;SE(
7) 9eonard =?, Morris AAM( Diagnosis and earl, management of in)orn errors of
meta)olism presenting around the time of )irth( Acta Pediatrica 200&@ %" &41<(
E+ 5hristodoulou =, 2ilc#en A( Perimortem la)orator, in3estigation of genetic
meta)olic disorders( Semin Neonataol 200<@ " 2C%42E0(
+ Summar M( 5urrent strategies for the management of neonatal urea c,cle
disorders( = Pediatr 2001@ ;E" S;04S;(
10+ 9eonard =?, Morris AAM( Drea c,cle disorders( Semin Neonatol 2002@ C" 2C4;%(
11)de Aauln, 8L, Saudu)ra, =M( Aranched4chain organic acidurias( Semin Neonatol
2002@ C" &%4C<(
12+ Saudu)ra, =M, Nassogne M5, de 9onla, P, 1ouati /( 5linical approach to
inherited meta)olic disorders in neonates" an o3er3iew( Semin Neonatol 2002@ C"
;41%(
1;+ 2olf NI, Aast 1, Surtees S( !pileps, in in)orn errors of meta)olism( !pileptic
Disord 200%@ C*2+" &C4E1(
1<+ Ha)ra M( Dietar, management of In)orn errors of meta)olism( Indian = Pediatr
2002@ &" <214<2&(
1%+ Arad, 7L, Schiffmann 7( !n0,me4replacement therap, for meta)olic storage
disorders( 9ancet Neurol 200<@ ;" C%24C%&(
1&+ Saudu)ra, =M, Sedel 6, 2alter =8( 5linical approach to treata)le in)orn
meta)olic diseases" an introduction( = Inherit Meta) Dis 200&@ 2" 2&142C<(
1C+ !lias S, Simpson =9, Shulman 9P( 1echni-ues for prenatal diagnosis( In" 7imoin
D9, 5onnor =8, P,erit0 7!, Horf A7 eds( !mer, and 7imoinFs Principles and
practice of medical genetics( 5hurchill49i3ingstone, 9ondon 2002" E024E2%(
)able +: Clinical pointers towards specific IEM2s
Clinical finding Disorder
5oarse facies 9,sosomal disorders
5ataract /alactosemia, Gellweger s,ndrome
7etinitis pigmentosa Mitochondrial disorders
5herr, red spot 9ipidosis
8epatomegal, Storage disorders, urea c,cle defects
7enal enlargement Gellweger s,ndrome
!c0emaBalopecia Aiotinidase deficienc,
A)normal #in#, hair Men#e disease
Decreased pigmentation Phen,l#etonuria
8iccups Non#etotic h,pergl,cinemia
Lphthalmoplegias MSDD, Non#etotic h,pergl,cinemia
)able 4: Categori-ation of neonatal IEM %sing metabolic screening tests
Acidosis Ketosis 0actate Ammonia Diagnosis
4 O 4 4 Maple s,rup urine
disease
O OB4 4 OB4 Lrganic aciduria
O OB4 O 4 9actic acidosis
4 4 4 O Drea c,cle
4 4 4 4 Non4#etotic
h,pergl,cinemia , sulfite
o.idase deficienc,,
pero.isomal,
Phen,l#etonuria,
galactosemia
!ig +: Approach to newborn with s%spected metabolic disorder
$%spected Metabolic Disorder
Plasma N8
;
8igh Normal
Alood p8 : 5L
2
Alood p8 : 5L
2
Normal Acidosis Normal
*PHD, NH8, /alactosemia,
Pero.isomal disorders,
Aminoacidopathies+
No #etosis No #etosis
Hetosis with or without
9actic acidosis
Urea cycle defect FAOD Organic acidemias
Mitochondrial disorders
Plasma citrulline

*P1000 QmolB9+ 2%4%0QmolB9+ *Dndetecta)le+
ASA deficienc, Drinar, ASA Drinar, orotic acid
*citrullinemia+
O 4 O 4
ASA9 deficienc, 18AN L15 5PSBNA/S
*ASAuria+ deficienc, deficienc,
*A))re3iations" 6ALD" fatt, acid o.idation defects, PHD" Phen,l#etonuria, NH8"
Non#etotic h,pergl,cinemia, ASA" Argininosuccinic acid, L15" Lrnithine
transcar)amo,lase, 5PS" car)amo,l phosphate s,nthetase I@ NA/S" N4acet,lglutamate
s,nthetase, 18AN" transient h,perammonemia of new)orn, ASA9" argininosuccinic acid
l,ase+
!ig%re 4: Approach to newborn with persistent hypoglycemia and s%spected IEM
8,pogl,cemia
Drine nonglucose reducing su)stances
Present A)sent

Drine #etones

Positi3e Negati3e
/l,cogen storage 6att, acid
Diseases L.idati3e defects
/luconeogenic defects Hetogenesis defects
/alactosemia Lrganic acidemias 8,perinsulinism
Appendi5: Commercially aailable form%lations %sed in IEM
Co6factor )rade name' form%lation
P,rido.ine 1a) Aenadon *<0mg+ *Nicholas Piramal+,
In> ?itneurin *1 ampoule contains %0 mg
p,rido.ine+
8,dro.,co)alamin *?itamin A12+ In> 1rineurosol *1000mcgBml+
*1ridoss 9a)oratories+
1hiamine 1a) Aenalgis *C% mg+ *6ranco India+
7i)ofla3in 1a) 7i)ofla3in *% mg+ *Shre,a+
Aiotin 1a) !ss3it *%mg, 10mg+ *!copharma+
5arnitine S,rup 945arnitor *%mlR%00 mg+, 1a) 94
5arnitor *%00 mg+, In> carnitor *1gB%ml+
*!lder+
6olinic acid 1a) 9eu#orin *1% mg+ *Samrath+
Sodium Aen0oate Satchet 20g *8esh 5o(+
Arginine A7/4 Satchet *;g+ *No3eau Medicament+
5oen0,me J 1a) 5oJ ;0 mg, %0 mg( *Dni3ersal
Medicare+

Inborn Errors of Metabolism

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Inborn Errors of Metabolism

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AIIMS- NICU protocols 2010

Approach to Inborn Errors of Metabolism Presenting in the Neonate

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