28/10/2019

Question 1

Fabry disease. Short simple points about it.

Answer 1

• X-linked inborn errors of glycospingolipid metabolism.
• Lysosomal storage disease.
• caused by absent or deficient activity of alphal-galactosidase A on chromosome 22
• enzyme defects causes accmulation of glycosphingolipids in plasma and lysosomes of vascular endothelial and smooth muscles cells, heart myocytes and renal odocytes. So it can lead to small vessel occlusion and ischemia.
• 2 major phenotypes:
  
  • classic: absent, telangiectatic skin lesions/angiokeratomas, hypohydrosis, corneal and lenticular opacities
  • late onset: 4-8th decades, deficient, cardiac dsiease and/or renal failure
• Fabry crises: most debilitating symptom, due to pain. Crises lasts from mins to several days> burning pain in hands, feet, and proximal extremeties. Associated with fever, fatigue, exercise.
• Treatment: phenytoin and carbamazepine for acroparesthesias and fabry crisis
• renal transplantation for renal failure
• Enzyme replacement available.

Question 2

What is the differential for Angiokeratomas?

Answer 2

• fucosidosis
• aspartylglycosaminuria
• late-onset GM1 gangliosidosis
• galactosialidosis
• sialidosis

Question 3

What are symptoms fo autonomic failure?

Sympathetic?

Parasympathetic?

Enteric

Answer 3

• Sympathetic: orthostatic hypotension, anhidrosis
• Parasympathetic: dry mouth, dry eyes, urinary retention, slugghlish pupillary light response, fixed heart rate
• Enteric: GI dysmotility, early satiety, abdo pain, vomiting, diarrhoea, constipation

Question 4

What are causes of autonomic failure?

• Immune mediated?
• Systemic disorders?
• Inherited?

Answer 4

• Immune mediated: GBS (65% have dysfunction), POTS, autoimmune autonomic ganglionopathy
• Systemic disorders: diabetes mellitus, paraneoplastic, mitochondrial cytopathies
• Inherited: Charcot Marie, Fabry’s disease

Question 5

Neural tube developmental abnormalities

What does failure of closure of rostral neuropore cause?

What does failure of closure of caudal neuropore cause?

Answer 5

1. Anencephaly, cephalocoele
2. Spina bifida
   
   1. spina bifida occulta (vertebral arch defect)
   2. Meningocoele (dura+arachonoid herniation)
   3. Meyelo

Question 6

List spinal cord malformations (x4) and briefly describe them

Answer 6

• Diastematomyelia
  
  • spinal cord split in half at lower end by bony spicule or fibrous band
  • risk of tethered cord
• Syringomyelia/hydromeylia
  
  • dilated central canal or paracentral region
• Tethered cord
  
  • filum terminale fixed by fibrous band
• Spinal cord lipoma

Question 7

What condition is caused by failure of mesoderm to organise caudally?

Answer 7

spinal bifida

defect or absence of vertebral arches

Question 8

What are the 3 types of spina bifida?

Answer 8

• Myelomeningocoele (spinal cord and meninges protrude out, vertebral defect, held together by skin in severe cases/in really severe cases no skin at all = open spina bifida)
  
  • symptoms: loss of sensation, paralysis
  • open SB: damage to nerves and risk of infection
  • bladder and bowel movement problems
  • seizures
  • leg and foot deformity
  • Associations:Arnold chiari 2 malformation, cerebellar and brainstem tissue slip down into foramen magnum. Can cause hydrocephalus
• Meningocoele (meningeal cyst)
  
  • only meninges go thorugh the vertebral defect
  • least common
  • no symptoms
• Spina bifida occulta (most common and most mild)
  
  • hidden, prenatal tests don’t detect it mainly
  • no protrusion
  • found accidentally
  • Hair, dimple, birthmark above site of lesion
• Causes of all types unknown
  
  • Risk factors: folate /vitamin B9 deficiency, obesity, poor controlled diabetes, medications that interfere with folate metabolism (anti-seizure medication)
  • development of deform occur during 4th week
• Diagnosis for myelomeningcoele
  
  • prenatally with alpha fetoprotein in mother’s serum
  • other blood tests: HCG, inhibin A, estriol and ultrasound
  • amniocentesis
• Treatment:
  
  • prenatal surgery (to close the myelomeinogocoele)
  • postnatal surgery: days within surgery to minimise infections
  • Additional intervention: urinary cath, wheelchair or crutches due to paralysis

Question 9

Give example of disorder of prosencephalic development?

Answer 9

• Holoprosencephaly
• failure to separate forebrain into left and right hemispheres
• often midline brain and face abnormalities
• many due to abnormalities of the sonic hedgehog signalling pathway for ventral induction

Question 10

Answer 10

Question 11

Answer 11

Question 12

Overview of Neural Tube Defects

Answer 12

Question 13

Outline the Neurulation timeline

Answer 13

Question 14

Answer 14