Metabolics

Question 1

Adrenoleukodystrophy

Answer 1

Can’t break down VLCFA: accumulates in CNS, Leydig cells and adrenal cortex
Never occurs before 3
behavioural problems, seizures, sensory deficits, vegetative state in 1-2 years, adrenal insufficiency

MRI: Inflammatory demyelination. Looks like 2 white, spidery kidneys around the posterior ventricle

Question 2

Leigh Disease

Answer 2

Mitochondrial Disorder
Disorder of pyruvate metabolism

Starts in infancy.Feeding problems, Dev Delay, Maybe seizures/weakness/hypotonia
SIGHING
Lactic Acidosis

MRI: Demyelination, gliosis, necrosis. In Basal Ganglia and Brainstem.

Question 3

Metachromatic Leukodystrophy

Answer 3

Lysosomal Storage Disorder

Can be infantile, juvenile, adult
Accumulation of fats leads to destruction of the myelin sheath
Developmental Delay. NO Seizures!
Hypotonic. No Reflexes. Dysarthric. 
Butterfly effect on MRI
Optic Atrophy

Question 4

Urea Cycle Disorders

0. Examples
1. Pathology
2. Presentation
3. Investigations
4. Acute Management
5. Chronic Mgmt

Answer 4

0. OTC (x-linked and not on NBST)
1. Can’t break down ammonia in the urea cycles, so it build’s up
2. Encephalopathy, lethargy, vomiting, cerebral oedema, coma
3. VERY high ammonia, respiratory alkalosis to acidosis, UOA shows orotic acid
4. Stop protein, 10% Dex, Ammonia Scavengers (Sodium benzoae, phenylbutyrate, arginine
5. Don’t fast, low protien diet, arginine or citrillune supplements, a phenylbutyrate

Question 5

Batten Disease

Answer 5

A Neuronal Cell Lipofuscinoses (the most common)
Starts at 5-10y
Vision problems and seizures
Fatal!

Question 6

MELAS

Answer 6

Recurrent stroke like episodes
Lactic Acidosis
Seizures
Other: eyes, DM, cardiomyopathy, Deaf, Proximal RTA

Question 7

Neimann-Pick Disease Pathology

1. A and B
2. C

Answer 7

1. A and B caused by mutations in the SMPD1 gene, leading to decreased ASM enzyme. As a results sphinomyelin cannot be broken down by ASM, and acumulates in the lysosome.
2. NPC1 and NPC2 gene mutation. Leads to build up of cholesterol in the lysosomes.

Question 8

Niemann-Pick Disease Presentation

1. A
2. B
3. C

Answer 8

1. By 3m: Hepatosplenomegaly (HSM) and growth retardation. Developmental regression. All have cherry red spot
2. Presents in childhood with HSM, ILD, low plt, slowed bone growth. 1/3 have cherry red spot and neuro symptoms.
3. Starts in childhood with ataxia, dystonia, SNGP, dysphagia, dysphonia and severe liver and lung disease.

Question 9

Tyrosinaemia

1. Classification
2. Deficiency in what enzyme?
3. Presentation
4. Investigation
5. Treatment

Answer 9

2. defective activity of fumarylacetoacetate hydrolase (FAH)
3. Recurrent hepatic crises leading to progressive liver disease, renal tubular dysfunction (Fanconi)
4. Succinylacetaone
5. Nitisinone.