Biochem Diseases

Question 1

A lysosomal storage disease that causes osteomalacia, aseptic necrosis of the femur, hepatosplenomegaly, and pancytopenia…

Name the disease, the defective enzyme, the inheritance pattern, and histological findings.

Answer 1

Gaucher disease

beta-glucocerebrosidase deficiency

autosomal recessive

Gaucher cells (lipid-laden macrophages that look like crumpled paper)

Question 2

Lysosomal storage disease that causes neurodegeneration, developmental delay, cherry-red macula, with no hepatosplenomegaly…

Name the disease, inheritance pattern, enzymatic defect and build-up product, and common histologic finding.

Answer 2

Tay-Sachs

autosomal recessive

hexosaminidase A deficiency –> build up of GM2 ganglioside

onion skin lysosomes on histology

Question 3

Infant has cherry red macula, hepatosplenomegaly, and focal neurologic deficits.

What disease is at the top of the differential? What is the inheritance pattern? What is the enzymatic defect? What histologic findings are seen?

Answer 3

Niemann-Pick disease

autosomal recessive

sphingomyelinase deficiency

foam cells on marrow biopsy

Question 4

4 month old with developmental delay, corneal clouding, hepatosplenomegaly.

What is the Dx?

What is the defect and build-up products?

What is the inheritance pattern?

What is an additional symptom that may occur?

Answer 4

Hurler’s syndrome

alpha-L-iduronidase deficiency -> build up of dermatan sulfate and heparan sulfate

autosomal recessive

GAGs can build up and occlude airway

Question 5

What disease is characterized by accumulation of galactitol in the lens –> infantile cataracts?

Name the enzymatic defect, inheritance pattern, and other clinical findings. What is the treatment?

Answer 5

Classic galactosemia

Defective galactose-1-P uridyltransferase –> no conversion of galactose-1-P to UDP-galactose

Other findings:

hepatomegaly

jaundice

intellectual disability

failure to thrive

increased e. coli sepsis risk

Treatment: limit galactose and lactose intake

Question 6

3 month old that has not been feeding well, has a musty odor on exam, seems pale, and has dry, flaky skin. What is the Dx? Name the inheritance pattern, defective enzyme, other symptoms, and the treatment.

Deficiency of what other nutrient may cause this disease?

Answer 6

Phenylketonuria

Autosomal recessive

Defective phenylalanine hydroxylase

Symptoms: musty odor, eczema, hypopigmentation, growth retardation, mental retardation, seizures

Treatment: tyrosine supplementation, avoid phenylalanine (artificial sweetners have aspartame, which has phenylalanine)

Deficiency of tetrahydrobiopterin can cause the disease