A 6-month-old girl is brought to the physician for evaluation of irritability and listlessness. Her parents are concerned that the child cannot sit or roll even though she was able to do so several weeks before. The child was previously healthy except for 2 prior respiratory infections. On examination, the patient is hypotonic with hepatosplenomegaly and a protuberant abdomen. She has a bright red macula on ophthalmologic examination along with cervical lymphadenopathy. All deep-tendon reflexes are diminished. Which of the following is the most likely cause of this child's developmental regression?
Niemann-Pick disease vs Tay-Sachs disease | ||
Diagnosis | Niemann-Pick disease | Tay-Sachs disease |
Pathology | Sphingomyelinase deficiency | β-hexosaminidase A deficiency |
Epidemiology |
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Onset | Age 2-6 months | |
Clinical features |
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This child's clinical presentation is consistent with Niemann-Pick disease (NPD) type A. There are 3 types of NPD, type A is the most severe; types B and C are milder. Types A and B are caused by sphingomyelinase deficiency.
NPD type A is a progressive, autosomal recessive condition that classically presents with loss of motor milestones at age 2-6 months. Characteristic findings include hepatosplenomegaly, a protuberant abdomen, hyporeflexia/areflexia, and a "cherry-red" macula on ophthalmologic examination. NPD type A is almost universally fatal by age 3 years. Currently, there is no treatment for this condition and supportive management is the mainstay of therapy.
(Choice A) Tay-Sachs disease is a progressive autosomal recessive condition caused by β-hexosaminidase A deficiency. Like NPD, Tay-Sachs disease also presents with loss of motor milestones, hypotonia, and a "cherry-red" macula. However, patients with Tay-Sachs disease have hyperreflexia (not areflexia) and no hepatosplenomegaly.
(Choice B) Galactocerebrosidase deficiency results in Krabbe disease, a rare autosomal recessive lysosomal storage disorder that presents early in infancy with developmental regression, hypotonia, and areflexia. A "cherry-red" macula and organomegaly are not seen.
(Choice C) Gaucher disease is due to glucocerebrosidase deficiency. Classic features include anemia, thrombocytopenia, and hepatosplenomegaly but not loss of milestones and a "cherry-red" macula.
(Choice D) Hurler syndrome (one of the mucopolysaccharidoses) is a lysosomal storage disorder due to lysosomal hydrolase deficiency. It presents at age 6 months-2 years with coarse facial features, inguinal or umbilical hernias, corneal clouding, and hepatosplenomegaly.
Educational objective:
Niemann-Pick disease type A is due to sphingomyelinase deficiency and presents at age 2–6 months with areflexia, hepatosplenomegaly, a "cherry-red" macula, and developmental milestone regression. Although Tay-Sachs disease presents in a similar manner, hepatosplenomegaly and areflexia are not seen.