Clinical Pediatric Neurology: A Signs and Symptoms Approach, 6th Edition

411 Pages·2009·20.09 MB·English

by  Gerald Fenichel MD

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CLINICALPEDIATRICNEUROLOGY: ISBN:978-1-4160-6185-4
ASIGNSANDSYMPTOMSAPPROACH
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Fenichel,GeraldM.
Clinicalpediatricneurology:asignsandsymptomsapproach/Gerald
M.Fenichel.—6thed.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-1-4160-6185-4
1. Pediatricneurology. I.Title.
[DNLM:1. NervousSystemDiseases–diagnosis.2. Child.3. Infant.WS340F333c2009]
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Preface
I have been writingand rewriting thisbook for over25 years. During that time,translations have
appearedinsixlanguages.Thewritingisaformofpost-graduateeducation.Itforcesmetokeep
upwiththegrowthofknowledgeinthefieldandthechangingwaysinwhichwethinkaboutdis-
eases. This text provides an approach to the common presenting problems of children with dis-
orders of the nervous system. The general organization is constant from one edition to the
next but the reader will find considerable change in the content. The text remains a manual of
practical information, much of it based on experience. I have felt free to present my own biases
concerning patient management in situations where a single standard of practice is not
established.
I am grateful to many of my colleagues and trainees at Vanderbilt for their input and advice.
The academic setting is the place where the teacher not only teaches, but also learns.
Gerald M. Fenichel, MD
vii
C h a p t e r
1
Paroxysmal Disorders
T
he sudden onset of neurological dysfunc- PAROXYSMAL DISORDERS
tion characterizes paroxysmal disorders. In
OF NEWBORNS
children, such events often clear completely.
Disturbance of ion channels (channelopathies)
Seizures are the main paroxysmal disorder of
are often the underlying cause (Turnbull
the newborn, occurring in 1.8 to 3.5 live
et al, 2005). Examples of channelopathies are
births in the United States, and an important
genetic epilepsies, migraine, periodic paraly-
feature of neurological disease (Silverstein
sis, and paroxysmal movement disorders.
and Jensen, 2007). Uncontrolled seizures
may contribute to further brain damage.
Brain glucose decreases during prolonged
APPROACH TO PAROXYSMAL
seizures and excitatory amino acid release
DISORDERS
interferes with DNA synthesis. Therefore, sei-
zures identified by electroencephalography
The diagnosing physician rarely witnesses the (EEG) that occur without movement in
paroxysmal event. The nature of the event newborns paralyzed for respiratory assistance
requiresinterpretingeventswitnessedbyathird are important to identify and treat. The
party,offeredbyafamilymember,or,worse,the challenge for the clinician is to differentiate
second-hand description that the parent heard seizure activity from normal neonatal move-
from the teacher. Never accept a second-hand ments and from pathological movements
description. Most “spells” are not seizures, and caused by other mechanisms (Table 1-1).
epilepsyisnotadiagnosisofexclusion.Seizures The long-term prognosis in children with
andsyncopearecommonlyconfused.Manypeo- neonatal seizures is better in term newborns
plestiffenandtrembleattheendofafaint.The than in premature newborns (Ronen et al,
criticaldistinctionisthatsyncopeisalwaysasso- 2007). However, the etiology of the seizures
ciatedwithpallorandseizuresneverare. is the primary determinant of prognosis.
Spells seldom remain unexplained when
viewed.Becauseobservationofthespelliscriti-
caltodiagnosis,askthefamilytovideothespell.
Most families either own or can borrow a cam- Seizure Patterns
era. Many have a camera in their cell phone.
Even when a purchase is required, a video is Seizures in newborns, especially in the prema-
often more cost-effective than brain imaging, ture, are poorly organized and difficult to dis-
and the family has something useful to show tinguish from normal activity. Newborns with
for the expenditure. Always ask the following
twoquestions:Hasthishappenedbefore?Does
anyoneelseinthefamilyhavesimilarepisodes? Table1-1 Movements That Resemble
Often,nooneoffersthisimportantinformation Neonatal Seizures
untilrequested.Episodicsymptomsthatlastonly
seconds and cause no abnormal signs usually Benignnocturnalmyoclonus
remainunexplainedanddonotwarrantlabora- Jitteriness
tory investigation. The differential diagnosis of Nonconvulsiveapnea
Normalmovement
paroxysmal disorders is somewhat different in
Opisthotonos
the neonate, infant, child, and adolescent and Pathologicalmyoclonus
presentedbestbyagegroups.
1
Chapter1 Paroxysmal Disorders
Rarely are such movements sustained for long
Table1-2 Seizure Patterns in Newborns
periods, and they do not “march” as though
spreadingalongthe motorcortex.Inanother-
Apneawithtonicstiffeningofthebody
wise alert and responsive full-term newborn,
Focalclonicmovementsofonelimborbothlimbson
oneside focal clonic seizures always indicate a cerebral
Multifocalcloniclimbmovements infarction or hemorrhage. In newborns with
Myoclonicjerking states of decreased consciousness, focal clonic
Paroxysmallaughing
seizures may indicate a focal infarction super-
Tonicdeviationoftheeyesupwardortooneside
Tonicstiffeningofthebody imposed on a generalized encephalopathy.
Diagnosis. During the seizure, EEG may show
hydranencephalyoratelencephalyarecapable a unilateral focus of high-amplitude sharp
of generating the full variety of neonatal sei- waves adjacent to the central fissure. The dis-
zure patterns. This supports the notion that charge can spread to involve contiguous areas
seizures may arise from the brainstem as well inthesamehemisphereandcanbeassociated
as the hemispheres. The absence of myelin- withunilateralseizuresofthelimbsandadver-
ated pathways for seizure propagation may sive movements of the head and eyes. Interic-
confine seizures arising in the brainstem. For tal EEG usually shows focal slowing or
the same reason, seizures originating in one amplitude attenuation.
hemisphere are unlikely to spread beyond Newborns with focal clonic seizures should
the contiguous cortex or to produce second- be evaluated immediately using computed
ary bilateral synchrony. tomography (CT) or ultrasonography to look
Table1-2listsclinicalpatternsthathavebeen forintracerebralhemorrhage.IftheCTisnor-
associated with epileptiform discharges in mal, contrast-enhanced CT or magnetic reso-
newborns. This classification is useful, but does nance imaging (MRI) 3 days later looks for
not do justice to the variety of patterns actually cerebral infarction. Ultrasonography is not
observed,nordoestheclassificationaccountfor useful in detecting small cerebral infarctions.
the 50% of prolonged epileptiform discharges
on the EEG without visible clinical changes.
Multifocal Clonic Seizures
Generalized tonic-clonic seizures do not occur.
Manynewbornssuspectedofhavinggeneralized Clinical Features. In multifocal clonic seizures,
tonic-clonicseizuresareactuallyjittery(see“Jitter- migratory jerking movementsare noted in first
iness”).Newbornsparalyzedtoassistmechanical onelimbandthenanother.Facialmusclesmay
ventilationposeaspecialprobleminseizureiden- beinvolvedaswell.Themigrationappearsran-
tification. In this circumstance, the presence of dom and does not follow expected patterns of
rhythmicincreasesinsystolicarterialbloodpres- epileptic spread. Sometimes prolonged move-
sure, heart rate, and oxygenation should alert ments occur in one limb, suggesting a focal
physicianstothepossibilityofseizures. rather than a multifocal seizure. Detection of
The term subtle seizures encompasses several themultifocalnaturecomeslater,whennursing
differentpatternsinwhichtonicorclonicmove- notesappearcontradictoryconcerningtheside
mentsofthelimbsarelacking.EEGmonitoring or the limb affected. Multifocal clonic seizures
has consistently failed to show that such move- are a neonatal equivalent of generalized tonic-
ments are associated with epileptiform activity. clonic seizures. They are ordinarily associated
One exception is tonic deviation of the eyes, with severe, generalized cerebral disturbances
whichisusuallyaseizuremanifestation. suchashypoxic-ischemicencephalopathy.
Thedefinitivediagnosisofneonatalseizures
often requires EEG monitoring. A split-screen Diagnosis. StandardEEGusuallydetectsmulti-
16-channel video EEG is the ideal means for focal epileptiform activity. If not, a 24-hour
monitoring. Epileptiform activity in the new- monitor is appropriate.
bornisusuallywidespreadanddetectableeven
whenthenewbornisclinicallyasymptomatic.
Myoclonic Seizures
Clinical Features. Brief, repeated extension
Focal Clonic Seizures
and flexion movements of the arms, legs, or
Clinical Features. Repeated, irregular slow alllimbscharacterizemyoclonicseizures.They
clonic movements (one to three jerks per sec- constitute an uncommon seizure pattern in
ond affecting one limb or both limbs on one the newborn, but their presence suggests
side) are characteristic of focal clonic seizures. severe, diffuse brain damage.
2
Chapter 1 Paroxysmal Disorders
Diagnosis. No specific EEG pattern is asso- of prematurity. Apneic spells are more com-
ciatedwithmyoclonicseizuresinthenewborn. mon during active than quiet sleep.
Myoclonic jerks often occur in babies born to Apneicspellsof10to15secondsaredetect-
drug-addicted mothers. Whether these move- ableat some time inalmost all prematureand
ments are seizures, jitteriness, or myoclonus some full-term newborns. Apneic spells of 10
(discussed later) is uncertain. to 20 seconds are usually associated with a
20% decrease in heart rate. Longer episodes
of apnea are almost invariably associated with
Tonic Seizures
a 40% or greater decrease in heart rate. The
ClinicalFeatures. Thecharacteristicfeaturesof frequency of these apneic spells correlates
tonic seizures are extension and stiffening of with brainstem myelination. Even at 40 weeks’
the body, usually associated with apnea and conceptional age, premature newborns con-
upward deviation of the eyes. Tonic posturing tinue to have a higher incidence of apnea
without the other features is rarely a seizure than do full-term newborns. The incidence
manifestation. Tonic seizures are more com- of apnea sharply decreases in all infants at
mon in premature than in full-term newborns 52 weeks’ conceptional age.
and usually indicate structural brain damage
rather than a metabolic disturbance. Diagnosis. Apneic spells in an otherwise
normal-appearingnewbornareasignofbrain-
stem immaturity and not a pathological con-
Diagnosis. Tonic seizures in premature new-
dition. The sudden onset of apnea and states
borns are often a symptom of intraventricular
of decreased consciousness, especially in pre-
hemorrhage and an indication for ultrasound
study. Tonic posturing also occurs in mature newborns, suggests an intracranial
hemorrhage with brainstem compression. An
newborns with forebrain damage, not as a sei-
immediate ultrasound examination should be
zure manifestation but as a disinhibition of
brainstem reflexes. Prolonged disinhibition performed.
Apneic spells are almost never a seizure
results in decerebrate posturing, an extension of
manifestation unless associated with tonic
the body and limbs associated with internal
rotation of the arms, dilation of the pupils, deviation of the eyes, tonic stiffening of the
body, or characteristic limb movements. How-
and downward deviation of the eyes. Decere-
ever, prolonged apnea without bradycardia,
brate posturing is often a terminal sign in
premature infants with intraventricular hem- and especially with tachycardia, is a seizure
until proven otherwise.
orrhage caused by pressure on the upper
brainstem (see Chapter 4).
Tonic seizures and decerebrate posturing Management. Short episodes of apnea do not
look similar to opisthotonos, a prolonged arch- require intervention.
ing of the back not necessarily associated with
eye movements. The cause of opisthotonos is
Benign Nocturnal Myoclonus
probably meningeal irritation. It occurs in
kernicterus, infantile Gaucher disease, and Clinical Features. Sudden jerking movements
some aminoacidurias. ofthelimbsduringsleepoccurinnormalpeo-
ple of all ages (see Chapter 14). They appear
primarily during the early stages of sleep as
Seizure-Like Events repeated flexion movements of the fingers,
wrists, and elbows. The jerks do not localize
Apnea consistently, stop with gentle restraint, and
end abruptly with arousal. When prolonged,
Clinical Features. An irregular respiratory pat-
the usual misdiagnosis is focal clonic or myo-
tern with intermittent pauses of 3 to 6 sec-
clonic seizures.
onds, often followed by 10 to 15 seconds of
hyperpnea,isacommonoccurrenceinprema-
ture infants. The pauses are not associated Diagnosis. The distinction between nocturnal
myoclonus and seizures or jitteriness is that
withsignificantalterationsinheartrate,blood
benign nocturnal myoclonus occurs only dur-
pressure, body temperature, or skin color.
Immaturity of the brainstem respiratory cen- ing sleep, is not activated by a stimulus, and
the EEG is normal.
ters causes this respiratory pattern, termed
periodic breathing. The incidence of periodic
breathing correlates directly with the degree Management. Treatment is not required.
3
Chapter1 Paroxysmal Disorders
Jitteriness especiallyinthefirst12hours,areusuallydueto
hypoxic-ischemicencephalopathy.Sepsis,menin-
Clinical Features. Jitteriness or tremulousness
gitis,andsubarachnoidhemorrhagearenextin
isanexcessiveresponsetostimulation.Touch,
frequency, followed by intrauterine infection
noise, or motion provokes a low-frequency,
andtrauma.Directdrugeffects,intraventricular
high-amplitude shaking of the limbs and jaw.
hemorrhageatterm,andpyridoxinedependency
Jitteriness is commonly associated with a low
arerelativelyrarecausesofseizures.
thresholdfortheMororeflex,butitcanoccur
Themorecommoncausesofseizuresduring
in the absence of any apparent stimulation
the period from 24 to 72 hours after birth are
and be confused with myoclonic seizures.
intraventricular hemorrhage in premature new-
borns, subarachnoid hemorrhage, and cerebral
Diagnosis. Jitterinessusuallyoccursinnewborns
contusion in large full-term newborns, and sep-
withperinatalasphyxiawhomayhaveseizuresas
sis and meningitis at all gestational ages. The
well.EEGmonitoring,theabsenceofeyemove-
cause of focal clonic seizures in full-term
ments or alteration in respiratory pattern, and
newbornsisalwayscerebralinfarctionorintrace-
thepresenceofstimulusactivationdistinguishjit-
rebralhemorrhage.HeadCTisdiagnostic.Cere-
teriness from seizures. Newborns of addicted
bral dysgenesis causes seizures at this time and
mothersandnewbornswithmetabolicdisorders
remainsanimportantcauseofseizuresthrough-
areoftenjittery.
outinfancyandchildhood.Allotherconditions
Management. Reducedstimulationdecreasesjit- arerelativelyrare.Newbornswithmetabolicdisor-
teriness.However, newbornsofaddictedmoth- dersareusuallylethargicandfeedpoorlybefore
ersrequiresedationtofacilitatefeedingandto theonsetofseizures.Seizuresarerarelythefirst
decreaseenergyexpenditure. clinical feature. After 72 hours, the initiation of
proteinandglucosefeedingsmakesinbornerrors
Differential Diagnosis of Seizures ofmetabolism,especiallyaminoacidurias,amore
importantconsideration.Table1-4outlinesabat-
Seizuresareafeatureofalmostallbraindisorders tery of screening tests for metabolic disorders.
inthenewborn.Thetimeofonsetofthefirstsei- Transmissionofherpessimplexinfectionoccurs
zureindicatestheprobablecause(Table1-3).Sei- duringdelivery,andsymptomsbeginduringthe
zures occurring during the first 24 hours, and second half of the first week. Conditions that
Table1-3 Differential Diagnosis of Neonatal Seizures by Peak Time of Onset
24Hours 72Hoursto1Week
Bacterialmeningitisandsepsis(seeChapter4) Cerebraldysgenesis(seeChapter18)
Directdrugeffect Cerebralinfarction(seeChapter11)
Hypoxic-ischemicencephalopathy Familialneonatalseizures
Intrauterineinfection(seeChapter5) Hypoparathyroidism
Intraventricularhemorrhageatterm(seeChapter4) Idiopathiccerebralvenousthrombosis
Lacerationoftentoriumorfalx Intracerebralhemorrhage(seeChapter11)
Pyridoxinedependency Kernicterus
Subarachnoidhemorrhage Methylmalonicacidemia
Nutritionalhypocalcemia
24to72Hours
Propionicacademia
Bacterialmeningitisandsepsis(seeChapter4) Tuberoussclerosis
Cerebralcontusionwithsubduralhemorrhage Ureacycledisturbances
Cerebraldysgenesis(seeChapter18)
Cerebralinfarction(seeChapter11) 1to4Weeks
Drugwithdrawal Adrenoleukodystrophy,neonatal(seeChapter6)
Glycineencephalopathy Cerebraldysgenesis(seeChapter18)
Glycogensynthasedeficiency Fructosedysmetabolism
Hypoparathyroidism-hypocalcemia Gaucherdiseasetype2(seeChapter5)
Idiopathiccerebralvenousthrombosis GM gangliosidosistypeI(seeChapter5)
1
Incontinentiapigmenti Herpessimplexencephalitis
Intracerebralhemorrhage(seeChapter11) Idiopathiccerebralvenousthrombosis
Intraventricularhemorrhageinprematurenewborns Ketotichyperglycinemias
(seeChapter4) Maplesyrupurinedisease,neonatal
Pyridoxinedependency Tuberoussclerosis
Subarachnoidhemorrhage Ureacycledisturbances
Tuberoussclerosis
Ureacycledisturbances
4
Chapter 1 Paroxysmal Disorders
(MSUD). Branched-chain ketoacid dehydroge-
Table1-4 Screening for Inborn Errors
nase is composed of six subunits, but the main
of Metabolism That Cause
abnormalityinMSUDisdeficiencyoftheE1sub-
Neonatal Seizures
unitonchromosome19q13.1-q13.2.Leucine,iso-
leucine,andvalinecannotbedecarboxylatedand
BloodGlucoseLow
accumulateinblood,urine,andtissues(Fig.1-1).
Fructose1,6-diphosphatasedeficiency
Glycogenstoragedisease,type1 Descriptions of later onset forms are given in
Maplesyrupurinedisease Chapters5and10.Transmissionofthedefectis
byautosomalrecessiveinheritance(Straussetal,
BloodCalciumLow
2006).
Hypoparathyroidism
Maternalhyperparathyroidism Clinical Features. Affected newborns appear
BloodAmmoniaHigh healthy at birth, but lethargy, feeding difficulty,
Argininosuccinicacidemia andhypotoniadevelopafteringestionofprotein.
Carbamylphosphatesynthetasedeficiency Aprogressiveencephalopathydevelopsby2to3
Citrullinemia days postpartum. The encephalopathy includes
Methylmalonicacidemia(maybenormal)
lethargy, intermittent apnea, opisthotonus, and
Multiplecarboxylasedeficiency
stereotyped movements such as “fencing” and
Ornithinetranscarbamylasedeficiency
Propionicacidemia(maybenormal) “bicycling.”Comaandcentralrespiratoryfailure
mayoccurby7to10daysofage.Seizuresbegin
BloodLactateHigh
in the second week and are associated with the
Fructose1,6-diphosphatasedeficiency
development of cerebral edema. Once seizures
Glycogenstoragedisease,type1
Mitochondrialdisorders begin, they continue with increasing frequency
Multiplecarboxylasedeficiency and severity. Without therapy, cerebral edema
becomesprogressivelyworseandresultsincoma
MetabolicAcidosis
anddeathwithin1month.
Fructose1,6-diphosphatasedeficiency
Glycogenstoragedisease,type1 Diagnosis. Plasma amino acid concentrations
Maplesyrupurinedisease
show increased plasma concentrations of the
Methylmalonicacidemia
Multiplecarboxylasedeficiency three branch-chained amino acids. Measures
Propionicacademia of enzyme in lymphocytes or cultured fibro-
blasts serve as a confirmatory test. Heterozy-
goteshavediminishedlevelsofenzymeactivity.
cause early and late seizures include cerebral
dysgenesis, cerebral infarction, intracerebral Management. Hemodialysis may be necessary to
hemorrhage,andfamilialneonatalseizures. correct the life-threatening metabolic acidosis.
Atrialofthiamine(10–20mg/kg/day)improves
Aminoacidopathies the condition in a thiamine-responsive MSUD
variant. Stop the intake of all natural protein,
MAPLESYRUP URINEDISEASE
and correct dehydration, electrolyte imbalance,
Analmostcompleteabsence(<2%ofnormal)of and metabolic acidosis. A special diet, low
branched-chain ketoacid dehydrogenase causes inbranched-chainaminoacids,maypreventfur-
the neonatal form of maple syrup urine disease ther encephalopathy if started immediately by
Maple syrup urine
Hypervalinemia disease
Valine (cid:2)-Keto-isovalerate Isobutyryl-CoA Methacrylyl-CoA
Valine
transaminase
Isoleucine (cid:2)-Keto-(cid:3)-methylvalerate (cid:2)-Methylbutyryl-CoA Tiglyl-CoA
Isoleucine
transaminase Isovaleric
acidemia
Leucine (cid:2)-Keto-isocaproate Isovaleryl-CoA β-Methylcrotonyl-CoA
Leucine
transaminase Branched-chain Isovaleryl-CoA
keto acid dehydrogenase
decarboxylase
Figure 1-1 Branched-chain amino acid metabolism. 1, transaminase system; 2, branched-chain
a-ketoacid dehydrogenase; 3, isovaleryl-coenzyme A (CoA) dehydrogenase; 4, a-methyl branched-chain
acyl-CoAdehydrogenase;5,propionyl-CoAcarboxylase(biotincofactor);6,methylmalonyl-CoAracemase;
7,methylmalonyl-CoAmutase(adenosylcobalamincofactor).
5
Chapter1 Paroxysmal Disorders
nasogastrictube.Newbornsdiagnosedinthefirst
2 weeks and treated rigorously have the best HCO (cid:4) NH (cid:4) 2 ATP
3 4 Mitochondria
prognosis.
CPSI N-acetylglutamate
Cytoplasm
GALdYeCfeINctEiEnNtChEePgHlyAcLinOeP-cAlTeaHvYing system causes Cphaorbsapmhaytle Citrulline Citrulline Aspartate
glycine encephalopathy (nonketotic hypergly- OTC
cinemia). Inheritance is autosomal recessive
Ornithine
(Hamosh, 2005). ASS
Clinical Features. Affected newborns are nor- Ornithine Argininosuccinate
mal at birth but become irritable and refuse
feeding anytime from 6 hours to 8 days after ASL
delivery. The onset of symptoms is usually
Urea Arginine Fumarate
within 48 hours, but delays of a few weeks ARG
occur in milder allelic forms. Hiccupping is
Figure 1-2 Ammonia metabolism and the urea
an early and continuous feature; some
cycle.CPSI,carbamylphosphatesynthaseI;OTC,
mothers report that the child hiccupped in
ornithine transcarbamylase; ASS, argininosuccinic
utero.Progressivelethargy,hypotonia,respira- acid synthetase; ASL, argininosuccinic acid lyase.
tory disturbances, and myoclonic seizures fol- ARG, arginase. ATP, adenosine triphosphate.
low. Some newborns survive the acute illness, (Adapted and redrawn from Summar ML: Urea
butmentalretardation,epilepsy,andspasticity cycle disorders overview. In GeneClinics: Medical
characterize the subsequent course. Genetics Knowledge Base [online database].
Inthemilder forms, theonsetofseizuresis Seattle,UniversityofWashington,August11,2005.
Availableat:http://www.geneclinics.org.)
after the neonatal period. The developmental
outcomeisbetter,butdoesnotexceedmoder-
ate mental retardation.
argininosuccinic acidemia, and argininemia
(arginase deficiency) are the disorders caused
Diagnosis. During the acute encephalopathy,
by defects in the enzyme systems responsible
theEEGdemonstratesaburst-suppressionpat-
forureasynthesis(Fig.1-2).Asimilarsyndrome
tern that evolves during infancy into hypsar-
resultsfromdeficiencyofthecofactorproducer
rhythmia. MRI may be normal or may show
N-acetylglutamate synthetase. Arginase defi-
agenesis or thinning of the corpus callosum.
ciencydoesnotcausesymptomsinthenewborn.
Delayedmyelinationandatrophyarelaterfind-
Ornithine transcarbamylase deficiency is an
ings. Hyperglycinemia and especially elevated
X-linked trait; transmission of all others is by
concentrations of glycine in the cerebrospinal
autosomal recessive inheritance (Summar,
fluid, in the absence of hyperammonemia or
2005).Theestimatedprevalenceofallureacycle
organicacidemia,establishthediagnosis.
disturbancesis1:30,000livebirths.
Management. No therapy has been proven
Clinical Features. The clinical features of urea
effective. Hemodialysis provides only tempo-
cycledisordersareduetoammoniaintoxication
raryreliefoftheencephalopathy,anddietther-
(Table1-5).Progressivelethargy,vomiting,and
apyhasnotprovedsuccessfulinmodifyingthe
hypotonia develop as early as the first day after
course. Diazepam, a competitor for glycine
delivery, even before the initiation of protein
receptors, in combination with choline, folic
feeding. Progressive loss of consciousness and
acid, and sodium benzoate, may stop the sei-
seizures follow on subsequent days. Vomiting
zures.Oraladministrationofsodiumbenzoate
and lethargy correlate well with plasma ammo-
atdosesof250to750mg/kg/daycandecrease
nia concentrations greater than 200mg/dL
theplasmaglycineconcentrationtothenormal
(120mmol/L).Comacorrelateswithconcentra-
range. This substantially reduces but does not
tions greater than 300mg/dL (180mmol/L)
normalizecerebrospinalfluidglycineconcentra-
andseizureswiththosegreaterthan500mg/dL
tion. Carnitine, 100mg/kg/day, may increase
(300mmol/L). Deathfollows quicklyinuntrea-
theglycineconjugationwithbenzoate.
tednewborns.Newbornswithpartialdeficiency
of carbamyl phosphate synthetase and female
UREACYCLE DISTURBANCES
carriers of ornithine transcarbamylase defi-
Carbamylphosphatesynthetasedeficiency,orni- ciencymaybecomesymptomaticafteringesting
thinetranscarbamylasedeficiency,citrullinemia, alargeproteinload.
6