LARGE NEUTRAL AMINO ACIDS PHENYLKETONURIA: Kathryn Moseley Assistant Professor of Pediatrics...
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Transcript of LARGE NEUTRAL AMINO ACIDS PHENYLKETONURIA: Kathryn Moseley Assistant Professor of Pediatrics...
LARGE NEUTRAL AMINO ACIDS LARGE NEUTRAL AMINO ACIDS PHENYLKETONURIA:PHENYLKETONURIA:
Kathryn MoseleyAssistant Professor of PediatricsDepartment of Pediatrics, Genetics DivisionUSC/Keck School of Medicine
High Hopes NPKUA Conference Jan. 2010
ObjectivesObjectivesPresent past and current
information on the use of LNAA and the rationale for treatment
Describe current experiences and present clinical data from recent studies
Summarize the most recent developments of this treatment and the cost/benefit of treatment
LNAALNAAChristensen, HN, 1953Andersen, AE, 1976Pratt, OE, 1980Berry, HK, 1990Lou, HC, 1994Pietz, J 1999Pietz, J. Lutz, 2003Koch, R 2003Matalon, R, 2006Matalon, R. 2007Schindeler, S, 2007
LARGE NEUTRAL AMINO ACID LARGE NEUTRAL AMINO ACID THERAPYTHERAPYValineMethonineIsoleucineLeucineHistidineThreonineTryptophanTyrosine Phenylalanine
Phenylketonuria
• Genetics: AR, 1: 12,000• Phenylalanine Hydroxylase def.• The enzyme expressed in the liver not in the brain. • Clinical presentation: MR, eczema, reduced skin pigmentation, behavioral abn.• DX –NBS (Phe/Tyr ratio >1.5). • Therapy: 1. Dietary therapy with phe restricted diet and special formula /LNAA Tx. (life long to prevent CNS insults) 2. BH4. • Monitoring: ~ monthly Phe/Tyr monitoring, • Prognosis: excellent if Tx initiated early and well controlled.
What causes the mental retardation???
Denmark 1985Denmark 1985Offered as an alternative for young
adults age 15 yearsComprised of LNAA with large
doses of Tyrosine and TryptophanSemi-free diet. Regular bread,
unlimited potatoes, rice, pasta. Small portions of meat are also allowed (50gm).
Not recommended for children or MPKU
LNAALNAAThe main difference between
LNAA therapy and standard therapy;
80% of protein comes from natural food, 20% comes from medical product
LNAA in the United StatesLNAA in the United StatesPheBloc tabletsNeoPhe tablets and powderLanaflex powderPreKUnil tablets
Large neutral amino acid Large neutral amino acid therapy and therapy and phenylketonuria: a phenylketonuria: a promising approach to promising approach to treatmenttreatment
Richard Koch, Kathryn Moselely, Shoji Yano, Marvin Nelson Jr, Rex A Moats
2003
Large Neutral Amino Large Neutral Amino Acids and Late Diagnosed Acids and Late Diagnosed Phenylketonuria: the Phenylketonuria: the California Late Treatment California Late Treatment ProjectProject
K Moseley, S Yano, C Azen, R Boles, R Koch
INTRODUCTIONINTRODUCTIONIt is estimated that there are
approximately 200 individuals with PKU residing in state institutions and group homes that are untreated. Many of these individuals exhibit mental retardation, seizures, hypotonia, and neurological deterioration.
However, based on our recent experience in treating these individuals, proper treatment can reduce negative behaviors, improve overall health and reduce costs related to care.
OBJECTIVESOBJECTIVESAssess health outcomes,
behaviors and cost benefit analyses in known PKU adults residing in California who are being treated with LNAA therapy.
Provide treatment intervention protocols and training manuals to facilitate community placement of those untreated with PKU
To provide continuing education and resources to health professionals and care providers
METHODSMETHODS14 late diagnosed individuals with PKU
were enrolled in this observational study to evaluate the use of LNAA therapy (11 completed)
Informational data gathered included medical history, past and current medications, current diet, IQ, behavioral data and health care costs.
Vineland Adaptive Behavior Scales was obtained before the intervention and after one year.
METHODS CONTINUEDMETHODS CONTINUEDCare providers used intermediate
monthly behavior check list to document behaviors.
Phe/tyr obtained monthly.Dietary intervention: Subjects
reduced natural protein intake to the RDI of 0.8g/kg. ◦LNAA tablets implemented to supply
enhanced amounts of tyrosine and tryptophan.
Phe
LNAA Status
Pre Post
Mea
n +
s.e
.
0
200
400
600
800
1000
1200
1400
Tyrosine
LNAA Status
Pre Post
Mea
n +
s.e
.
0
20
40
60
80
100
Phe/Tyrosine Ratio
LNAA Status
Pre Post
Mea
n +
s.e
.
0
5
10
15
20
25
30
35
CHANGE IN BLOOD CHANGE IN BLOOD LEVELSLEVELS
No significant change in blood phe levels◦36+/-591umol (p=0.84)
Significant increase in blood tyrosine levels 19+/-28umol (p=0.05)
Significant decrease in phe/tyr ratio -9+/-13umol (p=0.05)
CHANGE IN BEHAVIOR VS CHANGE IN BEHAVIOR VS CHANGE IN BLOOD CHANGE IN BLOOD LEVELSLEVELS
◦Correlation between increased tyrosine and improvement in daily living skills (p=0.027)
◦Sig correlation between increased tyrosine and less aggression towards others (p=0.037)
◦Decrease in phe/tyr ratio correlated with improvement in daily living skills (p=0.012)
PKU Late Tx ProjectPKU Late Tx ProjectBehavior Outcomes Behavior Outcomes
VINELAND - No sig improvement in the group as a whole◦Biggest change in DLS 7+/-13
(p=0.19) 1 pt declined, 2 had no change, 4 improved
OBSERVED BEHAVIORS – No sig improvement in the group as a whole◦Trends toward reduced numbers of
SIB and agression
Cost Benefit Analysis-Cost Benefit Analysis-DrugsDrugsCost before PreKunil
Cost after
PreKUnil
% change
$3672 $1810 ~50%
Savings/yr
~22,344
Cost/Benefit AnalysisCost/Benefit AnalysisAverage cost living in
Developmental Center $236,700 annually
Average cost living in a Board and Care facility $122,280
Yearly savings $114,420
SUMMARYSUMMARYImprovement in daily living skills
was significantly correlated with increased tyrosine and decreased phe/tyr ratio.
The cost for psychotropic medications decreased approximately 50%.
The cost of living in a board and care facility is less than half the cost of living in a development center.
SUMMARY CON’TThe use of LNAA has been shown
to improve blood amino acid profiles
Increase tyrosine and tryptophan blood levels
Decrease brain phe levels Well accepted by patients
ACKNOWLEDGEMENTSACKNOWLEDGEMENTSFrank D. Lanterman Regional
Center◦Diane Campbell Anand, Director
California Department of Human Subjects