Genetics E1- Inborn Errors of Metabolism

What are inborn errors of metabolism (IEMs)?

Absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite

Most IEMs follow _______

Autosomal recessive or X-linked recessive patterns

What systems are most commonly affected by IEMs?

Neurologic & gastrointestinal

What neurologic clinical manifestations can be seen with IEMs?

Lethargy, coma, seizures, developmental delays, neuropathy, hypotonia, myopathy, ataxia, & neuropsychiatric sx (behavior changes, mood disorders, cognitive decline)

What GI clinical manifestations can be seen with IEMs?

Vomiting/ poor feeding, organomegaly, jaundice

What kind of IEMs is hypertrophic cardiomyopathy seen with?

Conditions w/ impaired energy storage

Ex: lysosomal acid maltase deficiency (Pompe disease)

What kind of IEMs is dilated cardiomyopathy seen with?

Fatty acid & oxidation disorders, organic acidemias, mitochondrial disorders

What dysmorphic features are seen with peroxisomal disorders?

ex: Zellweger syndrome

High forehead, hypo plastic supraorbital ridges, epicentral folds, low & broad nail bridge, deformed ear lobes

What dysmorphic features are seen with lysosomal storage disease?

Course facial features

What dysmorphic features are seen with homocystinuria?

Long face, lanky body

What dysmorphic features are seen in Smith-Lemli-Opitz syndrome?

Cleft palate, CHD, hypospadias, polydactyly/syndactyly

What ophthalmologic manifestations can be seen with IEMs?

Cataracts, corneal opacities / clouding, cherry-red spots, retinitis pigments, dislocated lens

What dermatologic manifestations can be seen with IEMs?

Rashes, photosensitivity, hyperkeratosis, ichthyosis, skin ulceration, skin nodules, hypopigmentation, melanocytic nevi

What are examples of abnormal odors that can manifest in the breath, urine, perspiration, saliva, or cerumen of a patient with an IEM?

Maple syrup urine, mouse urine, musty, fruity / ammoniacal, cabbage-like, rotten eggs, malt or hops, cat urine, or fish like

What is the goal of newborn screening?

To detect life threatening or long term disorders before they become symptomatic

What might a delay in the diagnosis of an IEM result in?

Acute metabolic decompensation, progressive neurological injury, & death

Why is perinatal history usually normal with IEMs?

Any impaired metabolism is compensated by the mother

When evaluating IEMs, what might the patient history reveal?

Consanguinity (many are autosomal recessive), early childhood deaths in siblings, some perinatal issues such as low maternal estriol, dec fetal movement, & HELLP syndrome

What are examples of lab results that can be seen with different IEMs?

Metabolic acidosis, hyperammonemia, hypoglycemia, respiratory alkalosis, ketones, lactic acidosis