Inherited conditions Flashcards
Incidence of inherited metabolic disorder
1:1500
Clinical symptoms of inherited metabolic disorder
Poor feeding, vomiting
Lethargy
Seizures
Coma
Not responsive to glucose and calcium
Cystinuria
- Inheritance
- Definition
- Presentation
Autosomal recessive
- Mutation prevents reabsorption of basic/ positively charged amino acids.
Aminoaciduria
- Cysteine is not reabsorb in kidney properly= Excess cysteine into the urine which forms stones
- Deficiency in transport and metabolism of amino acids.
Stone locations:
- Kidney
- Ureter
- Bladder
Phenylketonuria
- Pathophysiology
- Genetics
Decreased metabolism of amino acid phenylalanine
- Phe accumulates in the blood and is toxic to the brain
- Defective phenylalanine hydroxylase= cannot break down into tyrosine.
- Tyrosine essential for catecholamine, melanins production.
Autosomal recessive
Phenylketonuria
- Signs and symptoms
Seizures, Tremors
Intellectual disability/ Low iQ
Microencephaly
Behavioural problems
Blonde hair, light skin (tyrosine needed for melanin production)
Musty odour
Urea cycle defects
- Defintion
- Signs and symptoms
Defects in urea cycle metabolites
- Glutamine
- Glutamic acid
- Aspartic acid
- Glycine
Signs and symptoms
- Occurs soon after birth
- Lethargy
- Poor feeding
- Seizures
- Coma
Glycogen storage disease type 1 (GSD)
- Definition
- Pathophysiology
- Signs and symptoms
Glucose-6-phosphatase deficiency
- Enzyme is required to hydrolysis G6P, to release glucose.
- lack of this enzyme causes glycogen to accumulate in glycogenolysis
Signs
- Hypoglycaemia
- Lactic acidosis (due to relying on anaerobic glycolysis)
- Lipidaemia
- Hepatomegaly
- Uricaemia
- Neutropenia
- Bruising
- Renal disease
Management of Glycogen storage disease type 1 (GSD)
Continuous feeds or corn starch
Limit other sugars- fructose, galactose, sucrose, maltose.
- This prevents more glycogen accumulation
Allopurinol
- Inhibits uric acid
Statins
- High cholesterol
Liver transplants
Galactosemia
- Definition
- Pathophysiology + genetica
- Signs and symptoms
- Treatment
Galactose 1 phosphate uridyl transferase (GAL1PUT) deficiency
- Causs build up of galactosemia
- Autosomal recessive
Galactose cannot be metabolise so builds up in tissue:
- Liver: hepaptomegaly, cirrhosis, jaundice
- Eyes: cataracts
- Brain: brain damage, seizures
- Hypoglycaemia: weight loss, vomitting
Treatment
- Galactose free diet
MCAD deficiency
- Definition
- Presentation
Medium-chain acyl-CoA dehydrogenase deficiency
- Fatty acid oxidation disorder
- Unable to breakdown medium chain fatty acid into acetyl-CoA
Presentation
- Hypoglycaemia when fasting/ ill (cannot form ketones from fatty acids)
- Reduced carnitine/ acyl ratio
- Elevation of medium-chain acylcarnitine
MCAD deficiency
- Management
Avoid fasting
Feed slow release carbs like starch to release glucose overnight.
Supplements
- carnitine
- Riboflavin
Mucopolysaccharidosis
- Definition
Inherited metabolic diseases caused by the absence/ malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans
- Causes GAGs to build up in cells, blood and connective tissues
Symptoms/signs
- Characteristic facial feature
- Mental retardation
- contractures
- Dysostosis
Cystinuria
- Management
Treating symptoms:
- Prevention of stones
- Good hydration
- Alkalisation of urine (citrate supplement, acetazolamide). - Chelation (removing cysteine)
- Using penicillamine - Surgery–> Lithotripsy
- Destroys stones
Phenylketonuria
- Management
Diet
- Low in phenylalanine
(soybeans, egg whites, shrimp, chicken breast, spirulina, watercress, fish, nuts, crayfish, lobster, tuna, turkey, legumes)
-
Replacement of cathecolamines/ Supplements
- L-DOPA
- 5-HT
- BH4 (co-enzyme for PAH that can be deficient)
Urea cycle defects
- Pathophysiology
Deficiency in enzymes that break down the metabolites of amino acid precursors
- Glutamine
- Glutamic acid
- Aspartic acid
- Gylcine
Causes ammonia accumulation= toxic to brain
Presents
- Hyperammoniaemia
- Alkalosis
- Normal LFT
Congenital hyperammonaemia type 1
- Defect
- Pathophysiology
- Genetics
Urea cycle defect
- Defect in carbamyl phosphate synthase
Prevens ammonia from being metabolised from glutamate= hyperammonaemia
Autosomal recessive
Congenital hyperammonaemia type 2
- Enzyme defect
- Pathophysiology
- Genetics
X-linked
- Most common type of urea cycle defect
Defective ornithine transcarbomylase
- Processes ornithine into cirtuline.
- Causes build up of ammonia
Citrulinaemia
- Genetics
- Mechanism
- Presentation
Autosomal recessive
Mutation of argininosuccinate synthase
- Forms argino-succinic acid from citrulline and aspartate
- Build up of ammonia
Presentation
- Brittle hair
Urea acid defects management
Dietary
- Reduced protein intake
Removal of toxic products
- Levulose (ammonia)
Removal of excess precursors
- Na Benzoate (glycine)
- Na phenylbutyrate (glutamate)
Replace urea synthesis intermediates
- Citrulline, arginine
Liver transplant
glycosaminoglycans
Long sugar chains in cells that help build tissues
- Bone
- Cartilage
- Skin
- Connective tissue
Hurler syndrome
- Definition
- Pathology
- Symptoms and signs
Mucopolysaccharidosis type I-
- Alpha-I-iduronidase deficiency= lysosomal storage disease
- Autosomal recessive
Signs and symptoms
- May be normal at birth
- Corsening of facial features
- large head, pominent frontal bones
- splenomegaly, hepatomegaly
Gargoyle cells
Cells swollen with excess lysosomes due to Hurler syndrome
- lack of alpha-1-duronidase enzyme
- Cannot breakdown GAGs
Examples of mucopolysaccharidosis
Hurler syndrome
Hunter’s disease
Sanfilippo
Mitochondrial disorders
- Inheritance
- Examples
Respiratory chain defects due to mutations in mitochondrial enzymes/ proteins
- Inherited from maternal mitochondria DNA
Examples
- Leighs’s disease
- Leber’s hereditary optic neurpoathy
- MELAS syndrome
Signs and symptoms
- Poor growth
- Muscle weakness
- Organ system disease
- Dementia
Peroxisomal disorders
Disorder of peroxisomes, required to oxidise many substrates.
Examples
- Zellweger’s
- Refusum
- Adrenoleucodystrophy
Causes accumulation of very long chain fatty acids in adrenal glands and peripheral nevers
Treatment
- Diet
- BM transplant
