Disorders of complex molecules

Niemann-Pick disease is a lysosomal storage disorder that involves a deficiency of (enzyme)

• Glucocerebrosidase

• sphingomyelinase

• iduronate 2-sulfatase enzyme (IDS)

• IUDA

Match the following

• for diagnosis of Gaucher disease

• Gaucher disease is a lysosomal storage disorder associated

• presence of cerebellar manifestations.

• Gene analysis is the gold standard

• autosomal recessive genetic inheritance

• Niemann-Pick disease type C is characterized by the

• with glucocerebroside accumulation

• Niemann-Pick disease is a lysosomal storage disorder of

__________cells, described as lipid-laden macrophages, are a characteristic of NIEMANN-PICK disease

__________cells, described as lipid-laden macrophages resembling crumpled tissue paper, are a characteristic of Gaucher disease

__________ bodies, seen on electron microscopy, are intracellular features of macrophages and neurons in NIEMANN-PICK disease.

• Tiger

• Zebra

• Negri

• Nissil

A 5-month-old girl undergoes evaluation for failure to thrive. The parents are concerned that she is no longer able to sit or roll over on her own, despite being able to a few weeks

ago. She was born at term with a birth weight of 2.5-kg (5.5-lb). Her current height and weight are below the 10th

percentile, while at her previous visit 2 months ago, she was in the 40th percentile for both. Vitals are within normal limits. Physical examination reveals marked hypotonia throughout, with decreased deep tendon reflexes

noted bilaterally in the upper and lower extremities. Abdominal examination notable for hepatosplenomegaly.

Fundoscopic examination is shown in the attached picture.

If further testing is performed, which of the following enzymes is most likely to be deficient in this patient?

• Alpha-galactosidase A

• Hexosaminidase A

• Galactocerebrosidase

• Glucocerebrosidase

• Sphingomyelinase

Answer explanation

This patient is being evaluated for failure to thrive. Her physical examination findings indicate hepatosplenomegaly and a cherry-red spot on the macula, a presentation that is consistent with Niemann-Pick disease, an autosomal recessive lysosomal storage disease.

A 1-year-old boy is brought to the clinic for evaluation of developmental regression and "odd appearance"

of his eyes. His parents state he was able to sit up on his own without support until a month ago, when they noticed that he could no longer sit up or roll over. Additionally, his parents state he has had recurrent respiratory infections, and they now notice a chronic nasal discharge. His birth was unremarkable. Vitals are within normal limits. Physical examination reveals a prominent forehead, flat nose bridge and enlarged lips, gums and tongue. Abdominal examination reveals a prominent forehead, flat nose ridge and enlarged lips, gums and tongue. Abdominal

examination reveals hepatosplenomegaly and an umbilical hernia. Ophthalmic examination is shown in the attached picture. Accumulation of which of the following metabolites is most likely present inthis patient's tissues?

• Heparan sulfate

• Glucocerebroside

• Ceramide trihexoside

• Galactocerebroside

• Sphingomyelin

Answer explanation

This patient, who is presenting with symptoms of corneal clouding, developmental delay, regression of previously attained developmental milestones, and hepatosplenomegaly, along with characteristic coarse facial features, likely has Hurler syndrome, a lysosomal storage disorder.

Children with PGAP3-CDG / Mabry syndrome have the following symptoms. Select all that apply;

• little to no speech development

• develop recurrent seizures in early childhood.

• Autistic behavior and sleep disturbances

• delay in reaching childhood milestones, such as sitting, crawling, and walking.

Answer explanation

All of these symptoms are common. The less common symptoms are hearing loss, cardiac problems.

Like most other disorders of glycosylation, PGAP3-CDG is an autosomal recessive disorder.

• True

• False

Hunter syndrome has a_______ course of progression than Hurler syndrome

• slower

• faster