An 11-year-old girl is evaluated for blurry vision. The patient was adopted internationally at age 9. She has no history of head or eye trauma or exposure to ionizing radiation. Motor and cognitive milestones have been achieved at the appropriate age. She has a good appetite and does not follow any specific diet. The patient takes no medications and has no allergies. Vaccinations are up to date. Vital signs are normal. She is at the 40th percentile for height and weight. Other than bilateral lens opacities, the rest of her examination is normal. Urine is positive for reducing substances. Deficient activity of which of the following enzymes is the most likely cause of this patient's eye condition?

Question

An 11-year-old girl is evaluated for blurry vision.  The patient was adopted internationally at age 9.  She has no history of head or eye trauma or exposure to ionizing radiation.  Motor and cognitive milestones have been achieved at the appropriate age.  She has a good appetite and does not follow any specific diet.  The patient takes no medications and has no allergies.  Vaccinations are up to date.  Vital signs are normal.  She is at the 40th percentile for height and weight.  Other than bilateral lens opacities, the rest of her examination is normal.  Urine is positive for reducing substances.  Deficient activity of which of the following enzymes is the most likely cause of this patient's eye condition?

Quizplus · Accepted Answer

11ec160b_369f_1823_9249_73f6a26ae8da_MD0001_00 Galactosemia results from deficiency of enzymes involved in galactose metabolism. First, lactose is broken down to galactose and glucose. Galactose is then phosphorylated to galactose-1-phosphate by the enzyme galactokinase (GALK). GALK deficiency causes galactose buildup and this excess is converted to galactitol, an osmotic agent that causes cataracts. Excess galactose also spills into the urine and causes it to test positive for a reducing substance. Serious systemic manifestations are not seen in GALK deficiency, and cataracts may be the only manifestation. In contrast, deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT) results in a more serious form of galactosemia. This is related to the accumulation of galactose-1-phosphate, a toxic metabolite that causes hepatic and renal dysfunction. Consequently, patients with GALT deficiency present early, in the neonatal period, with vomiting, lethargy, and failure to thrive. This patient's late presentation, normal growth, and the isolated presence of cataract are indicative of GALK deficiency. Infants born in the United States undergo routine newborn screens for detecting inborn errors of metabolism, such as galactosemia. (Choice A) Patients with aldolase B deficiency (hereditary fructose intolerance) cannot metabolize fructose and develop hypoglycemia, hypophosphatemia, and failure to thrive. Although reducing substances can be positive in the urine, cataracts are not present. (Choice B) Alpha-galactosidase A deficiency (X-linked recessive) results in Fabry disease, which can present with cataracts. However, neurological findings (eg, numbness, tingling, burning pain in the hands and feet) and angiokeratomas are also characteristic. (Choice C) Fructokinase deficiency leads to essential fructosuria, a benign condition that can result in a positive test for reducing substance but not cataracts. (Choice E) Glucose-6-phosphatase converts glucose-6-phosphate to glucose. Deficiency of glucose-6-phosphatase causes glycogen storage disease type 1 (von Gierke disease). The main clinical manifestations are hypoglycemia, lactic acidosis, hepatomegaly, and hypertriglyceridemia. Cataracts are not seen. (Choice F) Tay-Sachs disease results from hexosaminidase A deficiency. Affected infants have retinal cherry-red spots and loss of motor skills. Cataracts are not seen. (Choice G) Sphingomyelinase deficiency is seen in Niemann-Pick disease and leads to accumulation of sphingomyelin. Characteristics include hepatosplenomegaly, motor neuropathy, anemia, and macular cherry-red spots but not cataracts. Educational objective: Lenticular accumulation of galactitol in the lenses of patients with galactosemia can cause osmotic damage and development of cataracts. Cataracts may be the only manifestation of galactokinase deficiency. __________ References: Early cataract formation due to galactokinase deficiency: impact of newborn screening. (http://www.ncbi.nlm.nih.gov/pubmed/22154682)

An 11-Year-Old Girl Is Evaluated for Blurry Vision