Disorders of Lipid Metabolism Flashcards
Presentations of primary carnitine deficiency
- Hypoketotic hypoglycemia
- Hepatomegaly
- Encephalopathy
- Elevated transaminases
- Hyperammonemia
- Cardiomyopathy
- Pericardial effusion
- Muscle weakness
- Recurrent vomiting, diarrhoea
- Recurrent infections
- Hypochromic anaemia
Presentations of secondary carnitine deficiency
- Hypoketotic hypoglycemia in infancy
- Cardiac, skeletal muscle diseases
- Seizures
- Apnea
- Developmental delay
Causes of secondary carnitine deficiency
- Organic acidurias
- Respiratory chain, mitochondrial defects
- Renal Fanconi syndrome
- Drug induces - valproic acid
Methyl malonic aciduria
Methyl malonyl CoA mutase
- Ketoacidosis
- Hypotonia
- Hypoglycemia
- Hyperammonemia
- Hyperuricemia
Propionic aciduria
Propionyl CoA carboxylase
- Ketoacidosis
- Hypotonia
- Vomiting
- Lethargy
Medium chain acyl CoA dehydrogenase deficiency
Medium chain acyl CoA dehydrogenase
- Acidosis
- Hyperammonemia
- Hyperglycemia
- Fatty liver
Long chain acyl CoA dehydrogenase deficiency
Long chain acyl CoA dehydrogenase
- Non ketotic hypoglycemia
- Low carnitine
- High acyl carnitine
Glutaric aciduria
Glutaryl CoA dehydrogenase
- Ketoacidosis
- Convulsions
- Progressive neurological defects
- Cerebral palsy
Common characteristics of organic acidurias
- Accumulation of organic acids in body
- Acidosis
- Vomiting
- Convulsions
- Coma
Refsums disease
Phytanic acid hydroxylase or alpha hydroxylase Accumulation of phytanic acid 1. Polyneuropathy 2. Retinitis pigmentosa 3. Nerve deafness 4. Cerebellar ataxia
Ketosis
- blood level of ketone bodies normally <1mg/dl
- accumulates when rate of synthesis exceeds ability of extrahepatic tissues to use them
- ketonemia
- ketouria
- acetone breath
C/F of ketosis
- Metabolic acidosis
- Reduced buffers
- Kussmaul’s breath
- Acetone breath
- Osmotic diuresis due to ketonuria
- Sodium loss
- Dehydration
- Coma
Diagnosis of ketosis
Detection of ketone bodies in urine - Rothera’s test
Purple ring is seen
Management of ketoacidosis
- Insulin, glucose given intravenously
2. Maintenance of electrolyte and fluid balance
A teenage girl was brought to the hospital with complaints that she gets too tired and has muscle pains. A consulting neurologist found muscle weakness in arms and legs.
Biochemical investigations revealed elevated amounts of triglycerides esterified with primary long chain fatty acids.
Muscle biopsy report showed significant number of lipid vacuoles.
Carnitine deficiency
- Muscle weakness
- Myopathy
- Hypoglycemia
- Cardiomyopathy
Adrenoleukodystrophy
Deficient oxidation of VLCFA by peroxisomes
- X linked
- VLCFA accumulate in myelin sheaths and destroy them
- child dies during first decade of life
Zellweger syndrome
- proteins/enzymes not transported into peroxisomes
- formation of empty/ghost peroxisomes
- PUFA levels elevated
Lipid storage diseases
- lysosomal storage diseases
- failure of breakdown of sphingolipid due to enzyme deficiency
- can be detected by amniocentesis
- only 1 type of sphingolipid accumulates
- synthesis rate is not affected
- extent of enzyme def. is same in all tissues
1. Severe mental retardation
Gauchers disease
Beta glucosidase def. Glucocerebroside accuumulates 1. Hepatosplenomegaly 2. Bone erosion 3. Anaemia
Niemann Picks
Sphingomyelinase def. Sphingomyelin 1. Severe MR 2. CNS damage 3. Hepatosplenomegaly 4. Cherry red spot in macula
Krabbes leukodystrophy
Beta galactosidase def. Galactocerebroside 1. Severe MR 2. Total absence of myelin in CNS 3. Globoid bodies in white matter
Metachromatic leukodystrophy
Sulfatidesulfatase def. Sulphogalactocerebroside 1. Neurological deficit 2. Speech difficulty 3. Optic atrophy
Fabry;s disease
Alpha galactosidase def.
Ceramide trihexoside
1. Renal failure
2. Purplish papules seen
Tay Sachs
Hexosaminidase def. Ganglioside 1. MR 2. Cherry red spot in macula 3. Progressive deterioration
Multiple sclerosis
- demyelinating disease
- phospholipids are lost from white matter of CNS
- CSF contains excess phospholipids
A 63-year-old female presents to the clinic with recurrent midepigastric pain over the last 3 months. She reports some relief
shortly after eating, but then the discomfort returns. She has
tried various over-the-counter medications without relief. She
also reports feeling tired and has had to increase the amount of
ibuprofen needed for relief of her arthritis. She denies nausea
Gastric ulcer due to NSAIDs
- NSAID inhibit gastric enzymes needed for PG synthesis which protect gastric mucosa
