Pediatrics Leukodystrophies

Question 1

X-linked Adrenoleukodystrophy

Answer 1

• mutations in ABCD1 gene
• very long chain fatty acids accumulate in brain, adrenal gland and testes

Clinical:

1. ) adrenal insufficeincy
2. ) attention difficulties, cognitive decline and behavioural problems
   - speech and handwriting changes
3. ) progressive loss of speech, vision, and hearing
4. ) distal axonopathy

NEUROIMAING:
1.) predominant confluent T2 hyperintensity in parietalo-occiptal lobes and posterior corpus callosum

Need for cortical supplementation, stem cell transplant (cerebral cases)

Question 2

Krabbe disease

Answer 2

AR
4 phenotypes…add more info once you memorize this
-lysosomal storage disease and peripheral neuropathy
–deficiency of the enzyme galactocerebrosidase (GALC)

1. ) early onset infantile: prior to 6 months
   - irritability, developmental delay or regression
   - axial hypotonia
   - limb spasticity
   - optic atrophy
   - absent reflexes
   - microcephaly

2.) late onset infantile: 6 months - 3 years

3. ) Juvenile onset: 3 and 8 years
   - weakness
   - loss of skills
   - vision loss
   - regression
4. ) adult onset: older than 20 years
   - loss of manual dextierity
   - peripheral neuropathy
   - weakness

IMAGING:
1.) periventricular or parietoocipital
2.) corticospinal tract
?transplant

Question 3

Metachromatic leukodystrophy

Answer 3

AR

1. ) Late infantile
2. ) Juvenile
3. ) Adult

Clinical: regression in gross motor skills, peripheral neuropathy, and gall bladder polyps

IMAGING:

• confluent T2 hyper intensities surrounding frontal and parietal periventricular white matter
• tigroid: normal white matter alternates with hyperintense lesions

Question 4

AICARDI-GOUTIÈRES SYNDROME

Answer 4

Inflammatory disorder
Truncal hypotonia and spasticity, dystonia
Microcephaly
CHILBLAINS: vasculitic lesions, fingers/toes, pressure areas

Others: glaucoma, stroke, autoimmune diseases (SLE, hypothyroidism, diabetes, autoimmune gastritis, autoimmune hepatitis, antiphospholipid antibody syndrome)

CT head: CALCIFICATIONS: basal ganglia, deep white matter, thalamus, cerebellum dentate, temporal cysts, cerebral atrophy with ventricular enlargement

CSF: Lymphocytic predominance

Question 5

Cerebrotendinous xanthomatosis

Answer 5

AR: increase cholesterol and cholestanol; excretion of bile alcohols in urine and serum
xanthomas in tendons, skin, CNS, other organs

Neonatal: neonatal cholestatic jaundice
Childhood/Adolescence: bilateral catarct
Adults: cognitive dysfunction, ataxia, pyramidal signs

**premature cardiovascular disease, chronic diarrhea, tendon xanthomas, cholelithiasis

IMAGING: cerebellum white matter affected,

Question 6

Fabry disease

Answer 6

X-linked

• little alpha-galactocidase
• lipid storage disease

1. ) cutaneous: angiokeratomas (trunk, lips, groin), telangiectasias
2. )Renal: renal insufficiency, proteinuria
3. ) Eyes: corneal opacities, cataract
4. ) heart: cardiomyopathy and conduction block, left ventricular hypertrophy, CAD, heart failure
5. ) GI: nausea, vomiting, abdominal pain
6. ) Neurological:
   - PNS: small fiber neuropathy, acroparesthesias (painful neuropathic of limb pain), hypohidrosis
   - CNS: hearing loss, strokes–> posterior circulation, progressive lacunar infarct, vertigo, cognitive disturbances,

7.) Other: dolioachoectasia (extensive dilatation of vessels),

MRI: hyperintensities in the pulvinar region, diffuse white matter abnormalities

Workup: measure leukocyte GLA activity
Treatment: recombinant GLA available as enzyme replacement therapy

Question 7

McArdle disease

Answer 7

• AR
• Glycogen storage disease

Clinical:
1.) fatigue, exercise intolerance, myalgia, cramps, muscle swelling, fixed weakness

Muscle: 1.) stiffness 2.) pain 3.) weakness induced by brief periods of intense isometric exercise (i.e. weight lifting) or sustained exercise (jogging)

“Second wind” phenomenon: improvement in myalgias, muscle stiffness, initial fatigue, tachycardia (after 10 mins of exercise)

2.) acute kidney injury: prolonged exercise can lead to rhabdomyolysis

Labs: myoglobinuria, elevated CK
Genetic testing, forearm exercise test
KEY CLINICAL FINDINGS: Fatigability, myoglobinuria, rhabomyolysis