Tag Archives: Metabolic

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


Fatty Acid Oxidation Disorders

Various eg CoA disorders eg MCAD, LCAD, VLCAD; Carnitine disorders (transports fatty acids out of 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.


=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 happens in some parts of the world, as 1 gene responsible for majority of cases.

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).