Neonatal IEM

Question 1

Pompe’s disease

Answer 1

Glycogen storage disease type II; Autosomal recessive mutation in GAA gene

Lack of enzyme acid alpha-glucosidase to break down glycogen–> accumulation within lysosomes in the heart and other skeletal muscles

Progressive cardiomyopathy/failure and muscle weakness (AKA limb-girdle); usually die of cardiorespiratory failure by 1-2 years of age if infantile

Question 2

Treatment for Pompe’s disease

Answer 2

Alglucosidase alpha (recombinant human acid alpha-glucosidase); IV formulation (replaces defective enzyme activity)

Question 3

Zellweger’s Syndrome spectrum implicated genes?

Answer 3

PEX genes (affects the peroxisomes that break down very-long chain fatty acids)

Question 4

How to diagnose Zellweger’s spectrum disorders?

Answer 4

Obtain levels of VLCFA (24 carbons or longer)– if elevated, issue with breaking down VLCFA

Question 5

Clinical presentation of Zellweger’s spectrum

Answer 5

Significant hypotonia, enlarged and bulging fontanelles, seizures, profound feeding difficulties, micrognathia, broad nasal bridge, neuronal migration defects (diffuse polymicrogyria, hydrocephalus, abnormal myelination), developmental delay, eye and ear abnormalities.

Question 6

True or False. Dietary restrictions on VLCFAs aid in Zellweger’s spectrum.

Answer 6

False. Dietary restrictions are not shown to help with clinical picture.

Question 7

Recommended therapies for Zellweger’s syndrome?

Answer 7

Primary bile acid therapy (cholic acid)– reducing accumulation of bile acid precursors and severity of liver disease (bile acid biosynthesis disorder). Mostly supportive care.

Question 8

Does presence of elevated levels of VLCFAs diagnose Zellweger’s spectrum?

Answer 8

No, it is a screening test. Elevated levels can also be related to other mutations, need to get a confirmatory PEX gene panel.