Biochemistry and nutrition
USMLE® Step 1 style questions USMLE
A 7-month-old boy is brought to the clinic for evaluation of developmental delay. The child is breastfed, but the mother states that recently, he has been irritable and frequently has been having feeding difficulties. His parents have noticed that he is unable to roll over, while his older brother was able to sit up unassisted at the same age. He is of Ashkenazi Jewish descent. Vitals are within normal limits. Facial examination reveals no structural abnormalities. Neurological examination reveals symmetric peripheral neuropathy with diminished sensation to pain. Motor examination reveals spasticity, and muscle atrophy is noted in all extremities. Abdominal examination is unremarkable. Fundoscopy reveals optic atrophy. The family is instructed to return for further genetic testing; however, they are lost to follow-up. One year later, the child passes away due to aspiration pneumonia. Autopsy specimens reveal neural tissue with multinucleated macrophages that stain positive with Periodic acid–Schiff stain with widespread demyelinating changes. Accumulation of which of the following metabolites was responsible for this patient’s symptoms?
Krabbe disease is a rare autosomal recessive disease, in which there is deficiency in glucocerebrosidase enzyme and the accumulation of toxic myelin breakdown product inside cells. This results in progressive neurodegeneration in which early symptoms include vision problems, and balance issues. As the disease progresses, there may be inability to move, speak, or breathe. Most people with Krabbe disease die within two years of diagnosis.