Inborn Errors of Metabolism

Question 1

1. Metachromatic leukodystrophy
   
   1. What is the enzyme that is affected
   2. What are the clinical findings
   3. What are the three different forms of the disease?

Answer 1

1. Aryl Sulfatase A
2. clinical findings:
   
   1. leukodystrophy
   2. also affects liver, kidneys, pancreas, adrenal glands
3. Three Presentations

–Late infantile (18-24 months): Gait disturbance, hypotonia to hypertonia, regression, involuntary movements, neuropathy, cherry red spot

–Juvenile (4-10 years): Bradykinesia, poor school performance, ataxia, movement disorder, neuropathy, slower progression

–Adult: After puberty get personality and mental changes, cortical and cerebellar regression to frank dementia in third to fourth decade

Question 2

1. What disease does the following Image represent?
2. What inheritance pattern does it involve?
   
   1. What gene?
3. How do the Juvenile versus Adult forms present?

Answer 2

1. Alexander Disease
2. Autosomal Dominant mutation in GFAP, chromosome 17
3. Clinical findings:
   
   1. Psychomotor regression, spasticity, seizures
   2. Juveniles - ataxia and spasticity
   3. Adult - MS like presentation
   4. Macrocephaly

MRI shows diffuse demyelination in the frontal lobes

Question 3

DDx for IEM with Kinky hair?

Answer 3

1. Giant Axonal Neuropathy
2. Menke’s
3. Argyninnosuccinate lyase deficiency (Urea cycle)

Question 4

DDX for Retinitis Pigmentosa as part of disease

Answer 4

1. Mitochondrial (NARP, KSS)
   2.

Question 5

DDX for Cataracts

Answer 5

1. Down Syndrome
2. Myotonic Dystrophy
3. Peroxisomal
4. CTX
5. Galactosemia
6. NFII
7. Rubella
8. Wilsons
9. Fabry’s

Question 6

DDx for Optic atrophy

Answer 6

• “PICKL”
• Papilledema
• Infantile neuroaxonal dystrophy
• cockayne
• Krabbe, MLD, GM2, MPS
• Leber’s ON

Question 7

DDX for Hepatosplenomegaly

Answer 7

1. CDG
2. GMI
3. GM II (Tay sachs, and Sandoff)
4. Gaugher
5. MPS
6. Mucolipidosis
7. Neiman Pick disease
8. Pompei
9. Zellwegger
10. Wilson’s Disease

Question 8

CLinical Pearls : Skin

For the following disorders, what spot diagnoses in IEM can you think of:

• Eczema: _____, _____
• Excessive fat pads: ____
• Photosensitivity: _____, _____, _____
• Blonde Hair: ____

Answer 8

• •Eczema: Biotinidase, PKU
• •Excessive fat pads: CDG
• •Photosensitivity: Cockayne syndrome, Hereditary Tyrosinemia, Porphyria
• •Blonde Hair: PKU

Question 9

Clinical Pearls: Dysmorphism. name four disorders

Answer 9

1. Zellweger
2. MPS/oligossacharidosis
3. salla disease
4. PDH deficiency

Question 10

Skeletal abnromalities

• Dysostosis multiplex:
• Epiphyseal stippling:
• Wormian bones

Answer 10

• Dysostosis multiplex: MPS
• Epiphyseal stippling: Peroxisomal disorders
• Wormian bones

Question 11

Neuromuscular involvment: myopathy, cardiac, peripheral neuropathy

Answer 11

• Myopathy: Mitochondrial, GSD
• Cardiac: Mitochondrial, MPS, GSD
• Peripheral neuropathy: MLD, Krabbe, Mitochondrial, INAD, A beta lipoproteinemia

Question 12

Ocular findings in IEM?

Answer 12

Question 13

DDX Hearing Abnormalities

Answer 13

Question 14

DDx of metabolic acidosis

Answer 14

Question 15

DDX vomiting

Answer 15

Question 16

Hepatosplenomegaly

Answer 16

Question 17

DDx of IEM and Movement disorders (dystonia, choreoathetosis,etc)

Answer 17

Question 18

Short Stature

Answer 18

Question 19

Peripheral Neuropathy

Answer 19

Question 20

X-Linked

Answer 20

• PMD ( PLP1)
• X-ALD ( ABCD1)
• Fabry’s diesease ( Alpha-galactocidase)
• Hunter ( MPS-2)
• PDH
• OTC
• Creatine transport defect ( SLC6A8)
• Duchenne MD
• Aicardi
• IP
• RET
• Fragile X
• DCX
• FLNA

Question 21

Ashkenazi Jews

Answer 21

• Canavan
• Tay sachs disease
• NP-A
• Gaucher-1
• Familial dysautunomia
• Mucolupidosis
• CF
• Nemaline ( NEB-2)
• Cohen syndrome

Question 22

Amish Population

Answer 22

• •GA-1
• •AT
• •AGS
• •Amish infantile epilepsy syndrome
• •AR cerebellar atrophy
• •MPS- VII
• •LGMD 2H, 2I, 2A, 2E