A 16-year-old girl is brought to the clinic for evaluation of fatigue. The symptoms began about 6 months ago. She has had no fever, cough, vomiting, diarrhea, weight loss, or depressed mood. The patient is doing well in school. She also reports intermittent pain in her arms and legs over the past 2 years. The patient has no significant medical history and takes no medications. She was adopted at age 3, and her family history is unknown. Height and weight are at the 5th percentile for age. Temperature is 36.7 C (98.1 F), blood pressure is 110/70 mm Hg, pulse is 78/min, and respirations are 14/min. There is no nasal congestion, and the oropharynx appears normal. Cardiac examination shows normal S1 and S2 without murmurs. The lungs are clear without wheezing or crackles. The abdomen is soft and nontender. The liver is palpable 4 cm below the right costal margin, and the spleen is palpable 10 cm below the left costal margin. Skin examination shows no rashes or jaundice. Lymph nodes appear unremarkable. Pubic hair and breast development are consistent with Tanner stage 1. Laboratory results are as follows: Which of the following is the most likely diagnosis in this patient?

Question

A 16-year-old girl is brought to the clinic for evaluation of fatigue.  The symptoms began about 6 months ago.  She has had no fever, cough, vomiting, diarrhea, weight loss, or depressed mood.  The patient is doing well in school.  She also reports intermittent pain in her arms and legs over the past 2 years.  The patient has no significant medical history and takes no medications.  She was adopted at age 3, and her family history is unknown.  Height and weight are at the 5th percentile for age.  Temperature is 36.7 C (98.1 F), blood pressure is 110/70 mm Hg, pulse is 78/min, and respirations are 14/min.  There is no nasal congestion, and the oropharynx appears normal.  Cardiac examination shows normal S1 and S2 without murmurs.  The lungs are clear without wheezing or crackles.  The abdomen is soft and nontender.  The liver is palpable 4 cm below the right costal margin, and the spleen is palpable 10 cm below the left costal margin.  Skin examination shows no rashes or jaundice.  Lymph nodes appear unremarkable.  Pubic hair and breast development are consistent with Tanner stage 1.  Laboratory results are as follows:  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d65e_d9c7_bc81_c593290d8e7a_MD0003_00 This patient's presentation is most consistent with Gaucher disease, the most common lysosomal storage disease. In Gaucher disease, glucocerebrosidase deficiency results in the accumulation of glucocerebroside in lipid-laden macrophages of different tissues. The range of presenting manifestations can be broad due to varied organ involvement: Bone marrow infiltration results in thrombocytopenia and anemia, which is likely the cause of this patient's chronic fatigue. Leukopenia may also be present. Visceral organ involvement leads to splenomegaly, which is typically more prominent than hepatomegaly. Blood cell destruction due to splenic enlargement can also contribute to cytopenias. Skeletal involvement causes diffuse bony pain and may result in joint collapse or pathologic fractures. Delayed puberty (eg, absence of breast development by age 13) and poor growth (eg, ≤5th percentile for height and weight) are common findings in children. A high degree of suspicion for the diagnosis must be maintained both because of the varied manifestations and because onset may occur from infancy through adulthood. (Choice A) Anorexia nervosa should be considered in an adolescent with low weight, delayed puberty, and fatigue; anemia can also occur over time due to nutritional deficiencies. However, hepatosplenomegaly is inconsistent with this diagnosis. (Choice B) Fanconi anemia (inherited bone marrow failure due to defective DNA repair) causes short stature and anemia. In contrast to Gaucher disease, pancytopenia is common (ie, decreased leukocytes would be expected), and severe splenomegaly is atypical. Moreover, diagnosis is typically in early childhood due to associated congenital malformations (eg, hypoplastic thumbs) and developmental delays. (Choice D) Parvovirus infection can cause fatigue, joint pain, and cytopenias (from transient viral-induced bone marrow suppression); aplastic crisis can also occur in patients with an underlying hemolytic disorder (eg, sickle cell disease). However, these symptoms are typically acute and self-limited, unlike this patient's chronic symptoms. In addition, poor growth and pubertal delay raise concern for a systemic disorder, making parvovirus unlikely. (Choice E) Turner syndrome (XO genotype) can present as short stature and pubertal delay in girls. However, this patient's bone pain, hepatosplenomegaly, and cytopenias are not seen in this condition. Educational objective: Gaucher disease is a lysosomal storage disease that can present from infancy to adulthood and is due to glucocerebroside accumulation in macrophages of the bones, liver, and spleen. This accumulation results in cytopenias, bone pain, and hepatosplenomegaly. Poor growth and pubertal delay are other common findings in children. References: Hematological manifestations and complications of Gaucher disease. (http://www.ncbi.nlm.nih.gov/pubmed/33759681)

A 16-Year-Old Girl Is Brought to the Clinic for Evaluation