Metabolic disorders Flashcards
Phenylketonuria belongs to what group of disease?
Inherited Metabolic Disorders (IMD)
Mx of Phenylketonuria
Low phenylalanine diet
Types of Inherited Metabolic Disorder
Disorders of complex molecules
Intoxication
Energy insufficiency
Disorders of complex molecules def? Eg?
Disturbance to synthesis or catabolism of complex molecules
Eg lysosomal storage disorders
Intoxication def? Sx?
Sx due to acute or progressive intoxication leading to accumulation of toxins
Acute presentation: vomiting, coma, liver failure
Or chronic: progressive development delay
Energy insufficiency, where? Sx? Eg?
Defects expressed in liver, myocardium, muscle and brain Sx: - Hypoglycaemia - Hyperlacticacidaemia - Hypotonia
Eg. Fatty acid oxidation defects
Lysosomal storage disorder age of presentation
3-6 months
Presentation of lysosomal storage disorders
Neurological symptoms
Hepatosplenomegaly
Respiratory, cardiac and bone problems
Progression of lysosomal storage disorders
Slowly progress
Become life threatening
Mx of Lysosomal storage disorders
Supportive Enzyme replacement therapy Bone marrow transplant Substrate reduction therapy Gene therapy
Hyperammonaemia definitin
Premature neonate NH3 > 150 umol/L
Term neonate > 100 umol/L
Infant & child > 40 umol/L
Sx of hyperammonaemia
Acute tachypnoea Lethargy Vomiting Convulsions Encephalopathy
Acute Mx of hyperammonaemia
I. Stop protein intake II. High calorie infusion III. Arginine – to ‘drive’ urea cycle IV. Promote ammonia removal • Sodium benzoate/phenylbutyrate • Haemofiltration (NH3 >300 umol/L)
Chronic Mx of hyperammonaemia
I. Referred to paediatric metabolic clinic for longterm follow up
II. Low protein diet
III. Benzoate & Phenylbutyrate
IV. Arginine & Citrulline
V. Emergency regime to avoid catabolism during intercurrent illness
Long term consequences of hyperammonaemia / urea cycle defects
Significant developmental delay
Liver transplant required
MCAD
Medium Chain Acyl-CoA Dehydrogenase deficiency
Age of MCAD presentation
4 months - 3 yrs
MCAD definition
Metabolic crisis precipitated by fasting , illness or operation
Diagnosis of MCAD
– organic acids in urine
– blood spot acylcarnitines - increased octanoyl carnitine
– mutation analysis - common mutation K329E
Sx of Neonate/infant MCAD
Hypoglycaemia Irritability Tachypnoea Hypothermia Apnoea Seizures
Sx of Child MCAD
Hypoglycaemia Sweating Apathy Nausea Headaches Seizures Coma
Acute Mx of MCAD
– High dose glucose IV + insulin
– IV carnitine
Chronic Mx of MCAD
Avoid fasting
Diet low fat, high carbohydrate
Emergency regime
Oral carnitine
Response to fasting
Glycogenolysis + GNG
Alternative energy substrates - fatty acid/ketone oxidation
Albumin synthesis site
Liver
Albumin half life
~20 days
Function of albumin
Transport
Oncotic pressure
Normal albumin reference range
35 - 50 g/L
Causes of hypoalbuminaemia
Liver failure Malabsorption Sever illness - sepsis Inflammation - trauma Malignancy Nephrotic syndrome Burns Pregnancy CCF
Consequences of hypoalbuminaemia
Oedema
Calciuria - excess free calcium
Normal urine protein level
<150 mg/24h
Normal urine albumin level
< 30 mg/24h
Urine dipstick threshold for albumin detection
> 300 mg/L
Ix for proteinuria
Urine dip
Albumin creatinine ratio
Normal Albumin creatinine ratio
<3.0 g/mol
When shouldn’t albumin creatinine ratio be performed?
During acute illness
Phenylketonuria genetics?
Mutations of phenylalanine hydroxylase gene
Phenylketonuria diagnosis?
increased plasma phenylalanine (substrate) and reduced tyrosine (product)
