IEM

The parents of a 2-year-old girl, recent immigrants from Guatemala, bring their child to you for the first time. The child was born at term after an uncomplicated pregnancy and deliv¬ery, and her neonatal course was uneventful. She sat without support at 6 months of age, pulled to a stand at 10 months, and began walking at 14 months. She has a 10-word vocabulary, and she can drink from a cup and feed herself with a spoon. You also learn that a previous child in the family died at the age of 5 years from “heart trouble.” On physical examination, you note contractures of the lower extremities, stiffness of the hands, somewhat coarse facial features, and an enlarged liver and spleen. The child’s growth is within normal limits, and her ex¬amination is otherwise normal. What is the most appropriate next step to diagnose this child’s condition?
A. Abdominal computerized tomography
B. A brain MRI (magnetic resonance imaging)
C. Tests for a storage disorder
D. Chromosomes
E. Thyroid function studies

C. The enlarged liver and spleen, the coarse facies, and the his¬tory of the death of a previous child from “heart trouble” all point to a storage disorder as the most likely diagnosis in this case. Her joint contractures and hand stiffness may be explained by an abnormal metabolism, rather than a central nervous sys¬tem deficit as in cerebral palsy

You are asked by a general practitioner to see a 3-year-old boy admitted for failure to thrive, recent mild tachypnea, and cough. He has grown poorly throughout his first 3 years of life despite attempts at nutrition counseling. His parents report that he can no longer walk or feed himself, and his speech has become garbled with a hoarse voice. His physical examination reveals an afebrile, developmentally delayed boy with tachypnea. He is macrocephalic, has coarse facial features, has a normal eye examination. He has mild contractures of elbows and knees with decreased range of motion. His pulmonary examination is significant for fine crackles in the bases. His cardiac examination reveals a hyperactive pericordium with tachycardia. He has organomegaly on abdominal examination. As you review these findings with his mother relates that both of her sisters had sons with the same problem these boys died in their first decade of life, but no one knows why. She reports that her sisters have normal appearing, healthy daughters. The most likely disease afflicting this family is
A. Tay-Sachs disease
B. Gaucher disease
C. Hunter syndrome
D. Niemann-Pick disease
E. Morquio syndrome

C. This 3-years-old-child with failure to thrive, developmental regression, heart failure, organomegaly, and coarse facial features has a lysosomal storage disease. The familial pattern is consistent with an X-linked disorder, thus Hunter Syndrome (mucopolysaccharidosis [MPS] type II) is the most likely diagnosis. Most lysosomal storage diseases are autosomal recessive, but MPS II and Fabry disease are both X-inked.

The parents of an infant boy newly diagnosed with type 2 Gaucher disease have questions about the prognosis of their child. In addition, they want to know if they can have more chil¬dren and what the risk would be of having another child with the disease. You respond:
A. The child can be expected to have a good prognosis with enzyme replacement, low risk of recurrence in another child.
B. The child can be expected to have a good prognosis with enzyme replacement; 25% chance of recurrence in another child
C. A poor prognosis even with enzyme replacement can be expected, low risk of recurrence in another child.
D. A poor prognosis even with enzyme replacement can be ex¬pected; 25% chance of recurrence in another child.
E. A poor prognosis even with enzyme replacement can be ex¬pected; 100% chance of recurrence in another child.

D. Gaucher disease is inherited in an autosomal recessive manner. Therefore, each child of the same parents has a 25% chance of having the enzymatic defect leading to Gaucher disease. Infantile, or type 2, Gaucher disease has a poor prognosis. While enzyme replacement may help decrease organomegaly, the therapy does not seem to affect the neurologic symptoms. These patients frequently die in the first 2 years of life.

A 5-year-old boy is referred from the local elementary school for evaluation of behavioral difficulties. His development had been normal until 1 year ago when he became aggressive with his siblings. His father thought enrollment in kindergarten would help with discipline, but his behavior has worsened, he seems unable to learn many of the concepts taught in school, and seems to have lost some of his vocabulary. His father notes that the boy has a history of sleeping difficulty. Both parents are from the Cayman Islands, but the father knows of no other fam¬ily members with behavior difficulties or developmental delay. The physical examination reveals a boy with normal stature, coarse facial features, and hirsutism. He has decreased range of motion in his elbows and knees, abdominal organomegaly, and an inguinal hernia. The most likely diagnosis in this boy is:
A. Gaucher disease
B. Sanfilippo syndrome (MPS III)
C. Morquio syndrome (MPS IV)
D. Tay-Sachs disease
E. Fabry disease

B This child has a typical presentation of Sanfilippo syndrome; carrier rates in the Cayman Island are 1 in 10 for Sanfilippo type A. The behavior problems and developmental delay are frequently the first manifestation.

Parents bring an 8-month-old infant to your office for a child checkup. The parents recently emigrated from the middle east. The child has been in good health, but the parents are concerned the child has been losing developmental milestones. She can no longer reach for objects and no longer rolls over. On examination you witness exaggerated startle response stimulation. She has no abdominal organomegaly, but her fundoscopic examination reveals a bright red spot with a surround¬ing grayish halo in the center of her macula. This child most likely has:
A. Tay-Sachs disease
B. Gaucher disease
C. Hunter syndrome
D. Niemann-Pick disease
E. Morquio syndrome

A. This child likely has Tay Sach disease, a lysosomal storage disease common among those of Ashkenazi Jewish heritage. A cherry red spot in the center of the macula is characteristic. Cherry red spots may also be seen in some forms of Niemman-Pick disese; however, these patients typically have organomegaly.

A 4-month-old girl presents with extreme fussiness. Upon ex-amination she appears to have pain on palpation of the right leg and her sclera are notable for their bluish color. Radio¬graph reveals fracture of the right femur. The child’s parents deny any severe trauma. The child’s mother states that she had multiple fractures as a child. Family history is also likely to include:
A. Blindness
B. Hearing loss
C. Tall stature
D. Renal disease
E. Aortic aneurysm

B. This infant has features of osteogenesis imperfecta which is an autosomal dominant genetic disorder. Features include long bone fractures and vertebral injury with minimal trauma, short stature, deafness, and blue sclerae.