2 main groups – monoamine and GABA disorders.
Oculogyric crisis is characteristic! Can be mistaken for seizure.
So epilepsy with poor response to drugs and normal EEG?
Cerebral palsy with progression?
Tag Archives: Metabolic
Rhabdomyolysis
Muscle breakdown with release of products into blood stream that can cause acute renal failure. Can be associated with compartment syndrome, disseminated intravascular coagulation.
Typically occurs with crush injuries, sometimes seen with extreme endurance sports.
Can be infectious.
Recurrent seen with fatty acid oxidation disorders and Lipin 1 mutations.
Lipin 1 mutations
Autosomal recessive – heterozygotes may have exercise induced muscle symptoms or be prone to drug induced myopathy.
Basal CK high but spikes to over 100 000 with decompensation (infection, exercise, anaesthetic).
Treat crises with carbohydrates/intralipid.
Fabry’s disease
Alpha-galactosidase defect, one of the lysosomal storage disorders, with accumulation in various tissues.
X-linked but females get disease, so not correct to call them carriers.
Classically, “pain attacks”, affecting the extremities. In the abdomen, can mimic appendicitis. Due to accumulation in nerves. Since nothing to really see on examination, easily misdiagnosed as functional.
Other features:
- Renal impairment and failure.
- Angiokeratomas – a more specific feature, but not always present, and seen in other lysosomal disorders.
- Corneal changes
- Cerebrovascular and cardiac problems
[Omim]
Organic Aciduria/acidaemia
Inborn errors of metabolism.
Cause ketotic hypoglycaemia (ie formation of ketones eg beta-hydroxybutyrate is intact), but accompanied by acidosis (unlike glycogen storage disorders) and usually encephalopathy and hyperammonaemia eg methylmalonic acidaemia.
Fatty Acid Oxidation Disorders
Various eg CoA disorders eg MCAD, LCAD, VLCAD; Carnitine disorders (transports fatty acids into mitochondria). Present with severe hypoglycaemia.
There are related lipid storage disorders eg Fabry, Niemann Pick, MCLD where hypoglycaemia is not a feature.
AST/ALT raised, due to protein breakdown for gluconeogenesis. Acylcarnitines, organic acids abnormal.
MCAD
=Medium Chain Acyl CoA Dehydrogenase deficiency. Can be asymptomatic eg parents of newly diagnosed child, even with same gene defect! Crisis – vomiting, hypoglycaemia, hyperammonaemia, sudden death.
Diagnosis: Octanoyl- acylcarnitine increased.
Management is by avoidance of fasting , plus carnitine! Newborn screening started in UK in 2009.
Carnitine deficiency
In primary deficiency, there is non ketotic hypoglycaemia and cardiomyopathy, hepatomegaly, hyperammonaemia.
Various other abnormalities. Usually acylcarnitine, organic and amino acid analysis will clarify.
Glycogen Storage Disorders
Various. Not a problem of storing it, a problem of breaking it down! Classic type 1 is Glucose -6-phosphatase deficiency. Depending on the type, gluconeogenesis as well as glycogenolysis may be impaired – some of the enzymes are involved in both – so hypoglycaemia with ketones, lactate and triglycerides high. Liver becomes enlarged with excessive glycogen, Glucagon has no effect.
Managed by regular meals and extra complex carbohydrate eg cornstarch, as for ketotic hypoglycaemia.
Glycogen synthase deficiency is sometimes included. If you can’t make glycogen then you get an immediate glucose dip post prandially, you don’t get a big liver (obviously) but other mechanisms work ok so lactate is normal (cf typical Glycogen storage disorder).
Pompe disease is a lysosomal disorder, infantile form affects heart, neurodevelopment (enzyme treatment available).
McArdle syndrome is myophosphorylase defect – pain/weakness/cramps on exertion, myoglobinuria, second wind phenomenon (rapid recovery with rest).
Ketotic hypoglycaemia
What happens when you don’t eat enough and your carbohydrate stores run out! Typically due to illness, especially with vomiting.
But can be endocrine cause eg hypopituitarism, adrenal insufficiency. Growth hormone deficiency associated with recurrent hypoglycaemia even before growth failure apparent, associated with sudden death.
If you have excluded glycogen storage disorders (big liver, high lactate), glycogen synthase deficiency (normal liver, high lactate) and organic acidurias (acidosis, encephalopathy, usually high ammonia too), can be idiopathic (usually SGA at birth, thin, presents under 4yr, resolves by 7yr).
If ketones low and fatty acids high, then suggests fatty acid oxidation disorder (but usually just means hypoglycaemia was treated before sample was collected).
Regular meals + night time complex carbo snack, optimize nutrition, carbs if unwell eg Maxijul + Electrolade else Ribena/apple juice.