A 5-year-old girl is brought to the emergency department with sudden-onset weakness on her left side and slurred speech. She was sitting on the floor at home playing with her toys when she lost her balance and toppled over. Her father caught her and she did not hit her head. The patient has a history of developmental delay and "eye problems," for which she has been seen by an ophthalmologist. She has no other chronic medical conditions. She takes no medications and has no known allergies. Vital signs are normal. Weight is at the 5th percentile and height is at the 90th percentile. Examination shows an alert, fair-skinned, blue-eyed girl. She has long, thin arms and legs and a decreased upper-to-lower segment ratio. Left upper and lower deep-tendon reflexes are brisk; Babinski sign is upgoing on the left side. Joint hyperlaxity and skin hyperelasticity are also seen. Which of the following is the most likely diagnosis in this patient?

Question

A 5-year-old girl is brought to the emergency department with sudden-onset weakness on her left side and slurred speech.  She was sitting on the floor at home playing with her toys when she lost her balance and toppled over.  Her father caught her and she did not hit her head.  The patient has a history of developmental delay and "eye problems," for which she has been seen by an ophthalmologist.  She has no other chronic medical conditions.  She takes no medications and has no known allergies.  Vital signs are normal.  Weight is at the 5th percentile and height is at the 90th percentile.  Examination shows an alert, fair-skinned, blue-eyed girl.  She has long, thin arms and legs and a decreased upper-to-lower segment ratio.  Left upper and lower deep-tendon reflexes are brisk; Babinski sign is upgoing on the left side.  Joint hyperlaxity and skin hyperelasticity are also seen.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d6ee_48a2_bc81_036f34829d43_MD0003_00 Homocystinuria is an autosomal recessive disorder that results from errors in methionine metabolism secondary to cystathionine synthase deficiency. Patients with homocystinuria have a Marfanoid body habitus, including tall stature; long, thin limbs; joint hyperlaxity; ectopia lentis; and chest deformities. However, several clinical features are seen only in homocystinuria (Table). This child's fair hair and eyes, developmental delay, and cerebrovascular accident are virtually pathognomonic for homocystinuria. These patients may have thromboembolic events at any age due to pathologic changes in the vessel walls and increased adhesiveness of the platelets. Such events most commonly involve the cerebral vessels. Marfanoid body habitus The diagnosis of homocystinuria is made based on elevated homocysteine and methionine levels. Treatment includes vitamin B6, folate, and vitamin B12 to lower homocysteine levels. In addition, antiplatelets or anticoagulation should be administered to prevent stroke, coronary heart disease, and venous thromboembolic disease. (Choice A) Ehlers-Danlos syndrome is a collagen disorder characterized by scoliosis, joint laxity, and skin hyperelasticity. Patients with this disorder do not have the disproportionately tall stature, lens dislocation, or hypercoagulability seen in homocystinuria. (Choice B) Fabry disease (α-galactosidase deficiency) is characterized by angiokeratomas, peripheral neuropathy, and asymptomatic corneal dystrophy. Patients may also develop renal and heart failure and are at risk for thromboembolic events. Other than thromboembolic events, this patient's clinical presentation is inconsistent with Fabry disease. (Choice D) Krabbe disease is an autosomal recessive lysosomal storage disorder caused by galactocerebrosidase deficiency. Clinical features include intellectual disability, blindness, deafness, paralysis, neuropathy, and seizures. These patients do not have hypercoagulability or increased stroke risk. (Choice E) Although this patient's body habitus and phenotypic features are consistent with Marfan syndrome, her developmental delay, fair complexion, and recent thromboembolic event are not consistent with the syndrome. (Choice F) Phenylketonuria is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase. Clinical features of phenylketonuria include intellectual disability, fair complexion, eczema, and a musty body odor. These patients are not at risk for hypercoagulability. (Choice G) Tay-Sachs disease is an autosomal recessive gangliosidosis caused by a deficiency of β-hexosaminidase A. Clinical findings include intellectual disability, weakness, seizures, and presence of a cherry-red macula on examination. These patients are not at risk for hypercoagulability. Educational objective: Homocystinuria is an autosomal recessive disorder caused by cystathionine synthase deficiency. In addition to Marfanoid body habitus, patients with homocystinuria also have intellectual disability, downward lens dislocation, and hypercoagulability. Treatment involves vitamin supplementation and antiplatelet or anticoagulation to prevent thromboembolic events. References: Newborn screening for homocystinuria. (http://www.ncbi.nlm.nih.gov/pubmed/23908001) Anaesthetic management of a young patient with homocystinuria. (http://www.ncbi.nlm.nih.gov/pubmed/23146854) Treatment of inherited homocystinurias. (http://www.ncbi.nlm.nih.gov/pubmed/23124942)

A 5-Year-Old Girl Is Brought to the Emergency Department with Sudden-Onset