lina, * 2008€¦ · lina, * 2008 2860 g, ga 38 weeks at age 84 hour seizure blood glucose 1.2...
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Lina, * 2008
2860 g, GA 38 weeks
At age 84 hour seizure
Blood glucose 1.2 mmol/l (=22 mg%)
Metabolic test regular (NH4, FFS, ßOHB, Cortisol, org.
acids)
Glucose response glucagon
diazoxide (15 mg/kg) resistent
[18F]F-DOPA PET was done at
home hospital: diffuse pattern
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euglycaemia with octreotide 20µg/kg*day s.c. pump
No further diagnosis until 7/2009
referred to Magdeburg
Lina, * 2008
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Mutational analysis: at age 13 months
ABCC8-mutation in child and father
c.2117 – 2A>T, mother neg.
L-Dopa-PET/CT at `Frankfurter Tor:
focal lesion in pancreatic tail
Laparoscopic focus resection (2 cm)
(W. Barthlen, Greifswald)
stabile euglycaemia
Lina, * 2008
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L. v Rohden: intraoperative ultrasound
focal Form
[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
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focal type
[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
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• [18F]F-DOPA emerged in single scans are
difficult to interpret
• Gallbladder, pancreatic head/ uncinatus
• Higher specificity has been experienced by
repeated images in case of focal uptake
• Accuracy of localization has been increased by
image recalculation
Localisation by F18-Fluoro-L-DOPA PET-CT
Problems:
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1.0
1.2
1.4
1.6
20 30 40 60
SU
V-ratio
time
special pattern in focal forms
head
head/corpus
corpus
corpus
cauda
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accuracy
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Intraoperative ultrasound
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
Between 2004 and 2013, a [18F]F-DOPA-
PET/CT was performed in 138 patients (58
girls) (median age: 0.53y; range: 0.09-30.35y.).
Mutation analysis of ABCC8 and KCNJ11 were
carried out in the index patient and their
parents.
Pancreatic surgery was done in 43%
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
focal uptake of [18F]F-DOPA in 33 %
localization of the lesion
Head: 31 %, head/corpus: 9 %
Corpus: 24 %, corpus/cauda: 4 %
Cauda: 31 %
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
Surgery
Histology: 93 % focal
Mutational analysis:
pat. heterozygous
ABCC8: 73 %
KCNJ11: 11%
Accuracy of localization, acc. to surgeon: 100 %
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
Surgery in patients with diffuse uptake of
[18F]F-DOPA: 18 %
Histology: 94 % diffuse
Mutational analysis:
heterozygous mutation in ABCC8: 41 %
comp. heteroz./ homozygous in ABCC8/
KCNJ11: 18 %
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[18F]F-DOPA-PET/CT in DTZ
`Frankfurter Tor´(W. Mohnike)
Surgery in
focal uptake of [18F]F-DOPA: 33 %
diffuse uptake: 12 %
out of all surgery:
sensitivity of focal: 100 %
specificity: 85 %.
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Many thanks!
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Diffuser Typ
homozygote / compound heterozygote
KATP
-Kanal-Mutation
Metabolopathien
(GLUD1, Glukokinase)
Syndrome (BWS)
? (50% aller CHI)
Fokaler Typ
KATP
-Kanal-Mutation
auf paternalen Allel + Verlust
maternaler Allele (11p15) in
der fokalen Region
Histologie
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Genetik der KATP-Kanalerkrankungen
KCNJ11 (Kir6.2)
ABCC8 (SUR1)
Chromosom 11
Autosomal-rezessiv
Diffuser Typ
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Genetik der KATP-Kanalerkrankungen Genetik der KATP-Kanalerkrankungen
KCNJ11 (Kir6.2)
ABCC8 (SUR1)
Chromosom 11
Heterozygote, paternal vererbte, rezessive Mutation
Fokaler Typ
„Second-Hit in Inselzelle bei paternal vererbter Mutation: 1:270
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Genetik der KATP-Kanalerkrankungen Genetik der KATP-Kanalerkrankungen
Heterozygote, paternal vererbte, rezessive Mutation
Fokaler Typ SNP rs75710 (Exon 33)
Mutation c.612C>A p.D204E
ABCC8 KCNJ11
DNA Pankreas normal
DNA Blut
DNA Pankreas Fokus
I.Wieland, Magdeburg; S. Vogelgesang, Greifswald
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Dopamindecarboxylase
F18-Fluoro-L-DOPA PET-CT
1. Pankreaszellen nehmen DOPA auf.
2. Dopamin ist Transmitter in neuroendokrinen
Geweben,
3. Konversion in Dopamin ist von der aromatischen
Aminosäuredecarboxylase abhängig.
Siemens Biograph PET/CT Scanner
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1. Klinisches, genetisches, morphologische
heterogenes Krankheitsbild
2. keine Differenzierung nach,
• Geburtsgewicht
• Glukosebedarf,
• Glukose / Insulin,
• Glukagonresponse
Zusammenfassung
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3.Genetisch kann in 50% der Fälle kein
ursächlicher Defekt nachgewiesen werden
4.1/3 Patienten haben einen umschriebenen
Fokus,
5.Charakteristisch ist paternale Mutation in
ABCC8 oder KCNJ11
6.in Cauda oder Corpus laparoskopische OP
Zusammenfassung
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