302 adult presentations of inborn errors of metabolism Flashcards
What are the different types of carbohydrate disorders?
Glucose – Failure of release from glycogen leads to fasting hypoglycaemia often from birth
Lactose – glucose + galactose – problems start with breast/milk feeding
Sucrose – glucose + fructose – problems start with weaning to solids
What is glycogen storage disease type 1 (GSD1)?
Glucose-6-phosphatase deficiency
Presentations: hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, hypertriglyceridemia
Treatment : Corn starch (slow absorption), soy milk, allopurinol (prevention hyperuricaemia)
Liver transplantation
What is McArdle’s Disease (GSD 5)?
Lack of muscle glycogen phosphorylase required to release glucose
Causes failure of lactate production on ischaemic exercise
Treatment: Aerobic exercise programmes
What is galactosaemia?
Galactose 1-PO4 uridyl transferase deficiency usually presents first week of life with:
-Failure to thrive, prolonged jaundice and hepatomegaly
If a galactosaemic child is given milk, unmetabolized milk sugars build up and cause damage to liver, eyes, kidney, and brain
Diagnosis clinically plus positive urine reducing substances but definitive test is to measure enzyme in RBCs
Treatment is life long diet free of galactose. Soy milk doesn’t contain lactose
What is Hereditary Fructose Intolerance?
Fructose-1-P aldolase deficiency
Causes accumulation of F-1-P causes inhibition of gluconeogenesis and glycogenolysis leading to hypoglycaemia and hepatotoxic effects
Diagnosis: Fructose tolerance test, liver biopsy for enzyme activity, genetic testing
Treatment: Avoidance of sucrose and fruit
How do inherited metabolic diseases present?
Most babies are full term, normal weight and no abnormal features as they are protected during pregnancy.
Symptoms usually develop in the first week of life and typically within 24 – 48 hours.
Observations:
-Abnormal smell – sweet, musty, cabbage-like amino-acid organic aciduria
-Dysmorphic features
-Cataracts – galactosaemia
-Hyperventilation – metabolic acidosis (organic acid disorders)
Common presentations:
Hypoglycaemia
Metabolic acidosis
Failure to thrive
Vomiting
Fits or spasticity
Hepatosplenomegaly
Prolonged jaundice
Funny smell
What are the first line tests for Inherited metabolic diseases?
Ammonia Level - Hyperammonaemia
Glucose - Hypoglycaemia
Bicarbonate - Metabolic Acidosis
-High Anion gap
-Ketones – present or absent
-Lactic acidosis
Urate – high or low
Neutropenia
Haemolytic anaemia
Megaloblastic anaemia
Coagulation defects
Organic acid and amino acid profiles
What is Cystinuria?
An inherited metabolic disorder characterized by excessive amounts of undissolved cystine in the urine, as well as three chemically similar amino acids: arginine, lysine, and ornithine.
Excess cystine in the urine can lead to the formation of crystals and (calculi) in the urinary tract system. Some people with cystinuria do not form stones, while others frequently form stones
SLC3A1 and SLC7A9 gene mutations result in the abnormal transport of cystine in the kidney
What is Phenylketonuria (pku)?
Phenylalanine hydroxylase deficiency
Diagnosis: Plasma Phe > 120 M
Treatment: Phenylalanine restriction, L-DOPA, 5- hydroxytryptophan folinic acid, tetrahydrobiopter
Blonde hair, blue eyes, neuropsychological problems – low IQ, impaired myelination
What is Tyrosinaemia?
Defect: fumarylacetoacetate hydrolase
Three Types, type 1 is most severe
Clinical presentations:
Failure to thrive, D&V, jaundice, ‘cabbage-like’ odour, liver failure, hepatocarcinoma, renal Fanconi syndrome
Treatment: NTBC (Nitisinone) inhibits the tyrosine pathway and diminishes toxic accumulation. Liver and kidney transplant
What are Urea Cycle Defects?
Total lack of enzyme is fatal
Causes high ammonia levels
Most severe defect carbamoyl phospahte synthetase 1
Presentation usually at birth:
Convulsions, lethargy, poor feeding, coma
Late presentation – hyperactivity, hepatomegaly, protein avoidance
Treatment:
-Reduction of dietary problem
-Removal of excess toxic products in this case ammonia
-Replacement of intermediates in urea synthesis which helps force what little enzyme is available to maximal activity.
-Use of pathway inhibitors
-Organ transplantation
What is Propionic acidaemia?
Defects in propionyl-CoA carboxylase
Clinical presentation:
Neonatal severe metabolic acidosis; vomiting, lethargy, hypotonia; recurrent episodic ketoacidosis, associated with protein feeding
Biochemical: High plasma glycine; urinary excretion of 3-hydropropionic acid, methylcitrate, and tiglyglycine
Treatment:
Dietary protein restriction; Biotin, L-Carnitine; Metronidazole to inhibit proprionic acid formation in the gut
What is Methylmalonic Acidaemia?
Clinical presentation:
Early onset severe metabolic acidosis; refusal to feed; vomiting, lethargy, hypotonia
Biochemical: Urinary excretion of methylmalonic acid; hyperammonemia
Defects could occur in one of the enzymes such as methylmalonyl-CoA mutase
Treatment: Dietary protein restriction; L-Carnitine; Metronidazole, Avoidance of fasting
What is Medium chain acyl-CoA dehydrogenase deficiency (MCADD)?
Problems in metabolising fats
hypo-ketotic hypoglycemia
reduced total carnitine, free carnitine/acyl carnitine ratio
excretion of dicarboxylic acid (C6 -C10), acyl-carnitine ester, and glycine conjugates
