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.
=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.
In primary deficiency, there is non ketotic hypoglycaemia and cardiomyopathy, hepatomegaly, hyperammonaemia.
Various other abnormalities. Usually acylcarnitine, organic and amino acid analysis will clarify.
Similar incidence to CF in white populations. Protease inhibitor (PI), counteracts neutrophil elastase. Alleles include PiZ (defective), PiM (normal), PiNull (non functioning). Protein phenotype then described as Z, M, MZ, or None
- Double Null – very high risk of COPD but no liver disease!
- ZZ have high risk of COPD and liver disease.
- SZ also seen, risk of COPD.
The risk of emphysema is increased in males, in asthma and especially in smokers.
PiMZ genotype does not appear to predispose to chronic liver disease (in case control study). On the other hand, patients with decompensated liver disease (of any cause) were significantly more likely to have PiMZ, and particularly in HCV or NAFLD PiMZ was associated with more severe liver disease and need for liver transplantation. Suggests that if you have some other cause for liver disease, PiMZ will do less well.
J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S30-5. [pmid:16819398]
About 10% of children with Z phenotype have prolonged (obstructive) jaundice, most have abnormal LFTs at some point in first year of life. Only 2% progress to liver failure requiring transplantation. Risk of hepatocellular carcinoma also higher.
Augmentation therapy with IV AAT approved by FDA, expensive. May slow decline in lung function but not great evidence yet. No intended to treat liver disease.
Screening is really only useful in aggressive smoking and alcohol advice. Non-alcoholic fatty liver disease seems to worsen other causes of liver disease so avoidance of obesity seems important too.
Necrotizing panniculitis associated with AAT deficiency, seems to respond rapidly to AAT treatment.