1. Monitoring asymptomatic boys
Dr James Davison
Great Ormond Street Hospital London

2. Outline Adrenoleukodystrophy Assessments Outcomes Case report
Routes to diagnosis
Phenotypes
Assessments
Baseline
Monitoring
Outcomes
Case report

3. Peroxisome and X-ALD VLCFA

4. X-ALD – routes to diagnosis
Phenotypes
Route to Diagnosis
Pre-symptomatic
ABCD1 gene on X- chromosome
Adrenal disease
Antibody negative
Adrenal insufficiency
Childhood Cerebral ALD
Adrenomyeloneuropathy
Family cascade testing
(Newborn screening)
Adrenal presentation
Hypoglycaemia
Adrenal Crisis
Abnormal neurology
Behavioural, psychological, motor function, psychiatric

5. Baseline assessment VLCFA ABCD1 genetic testing Adrenal assessment
Diagnosis
Endocrine
VLCFA
ABCD1 genetic testing
Adrenal assessment
(Adrenal antibodies)
Neurological
Transplant baseline
Functional history
Neurological examination
Psychological assessment
MRI brain scan
Tissue typing
+/- donor search

6. Monitoring Annual assessment by endocrinologist
Endocrine
Neurological
Annual assessment by endocrinologist
Treatment as indicated by testing
Adrenal replacement therapy
Medical Alerts
Clinical evaluation every 6 months
Any new symptoms should prompt urgent re-evaluation
Behavioural
Cognitive
Physical-neurological

7. Monitoring MRI every 6 months 3-12 years MRI annual after 12 years
Neurological: imaging
Baseline MRI
MRI every 6 months 3-12 years
MRI annual after 12 years
*Earlier MRI if new symptoms.
If minor abnormalities- repeat MRI 2-3 months (GAD)
MRI: diffusion weighted imaging
± Gadolinium
Normal
Abnormal
±Early repeat
MRI every 6months until 12 years (annual after 12 years)*
Consider BMT

8. GOSH historic audit 31 males 9 advanced CCALD Baseline MRI 15 Abnormal
6 early CCALD
16 normal
10 BMT/ GT
Surveillance monitoring
4 Abnormal
12 On-going surveillance

9. GOSH case report Recurrent episodes of low blood sugar when unwell
5 year old boy
Recurrent episodes of low blood sugar when unwell
Synacthen test
Cortisol
0mins 178nmol/L
30mins 163nmol/L
60mins 157nmol/L
ACTH 1106ng/L
Started adrenal replacement therapy
Adrenal antibodies negative
VLCFA analysis
ABCD1: c.1849C>T, p.(Arg617Cys)
Parameter
Test 1
Test 2
Reference
C22 (umol/L)
43.3
47.6
( )
C24 (umol/L)
63.0
68.3
( )
C26
3.32
3.72
( )
C24/C22 ratio
1.45
1.43
( )
C26/C22 ratio
0.077
0.078
( )
Phytanate (umol/L)
2.89
6.11
( )
Pristanate (umol/L)
0.24
0.55
( )

10. GOSH case report Temper tantrums Normal neurological examination
5 year old boy
Baseline MRI brain
Temper tantrums
Normal neurological examination
Possible minor changes in corpus callosum

11. GOSH case report
Bone marrow transplant
10/10 matched unrelated bone marrow transplantation with busulphan/ fludarabine/ campath conditioning
Remains well several years post-transplant

12. Summary Professional awareness Newborn screening
Early Diagnosis
Monitoring
Professional awareness
Adrenal insufficiency  VLCFA
Newborn screening
Tissue typing early to avoid later delays
Endocrine
Neurological and MRI imaging
Capture early CCALD to permit timely intervention

13. Questions?