3

autosomal recessive disease

deficiency of glutaryl-CoA dehydrogenase

1 : 100 000 GCDH gene chromosome 19p13.2

#1 The accurate diagnosis of GA-I has important practical implications when devising treatment plans and giving appropriate information to children and their families.

#2 For mass newborn screening for glutaric aciduria type I determination of C5DC in DBS by MS/MS should be used

High excretors:

Amish Lumbee Irish Travellers

Low excretors:

Oji-Cree natives

#3 In a cohort with a high disease incidence due to a single

common GCDH mutation and a low excretor phenotype,

DNA based methods should be considered for newborn

screening. The use of MS/MS-based screening in such

populations will likely lead to false negative results

# 4: For the confirmation of a positive newborn screening result, a specific diagnostic workupis required, including a quantitative analysis of GAand 3-OH-GA

RT: 5.85 - 20.27

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20Time (min)

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

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100

Rela

tive A

bundance

8.99

16.60

14.68

17.00

14.1712.20

16.528.70 19.23

10.46 15.948.6719.14

16.16

10.1314.9113.41 18.74

6.88 13.69 15.527.78 9.44 17.12 17.9611.45 18.4112.48 19.2813.196.96 8.19 11.31 17.267.186.846.18 7.39

NL:3.43E8TIC F: MS 165_GAJOVA_Alzbeta

#5 …….GCDH gene mutation analysis, and/or enzyme analysis

#6 Metabolic treatment ……. by an interdisciplinary team….. (metabolic pediatrian, dietetist, nurse) + parents and patients training

#7 low lysine diet

#8. L-Carnitine

#9. Emergency treatment

#9. Emergency treatment should start withoutdelay and should be performed aggressively duringfebrile illness, surgery and immunization within thevulnerable period for acute encephalopathic crises (upto age 6 years)

#10 > 6 years …..

#15. Glutaric aciduria type I should be excluded in children with suspected shaken baby syndrome

#14. Children with subdural haemorrhage and/or bitemporal arachnoid cysts should be investigated for glutaric aciduria

GA I ?

GAI ?

#16 neurosorgical interventions - pediatric neurosurgeon

#17 monitoring in any age, in case of new complications

#18 Urine analysis of GA and 3-OH-GA is not informative for therapy monitoring

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