Transcript Case Study 38

Case Study 38
Henry Armah, M.D., M.Phil.
Question 1
Clinical history: 4-week-old male with severe hypotonia at birth. He
was a product of vaginal delivery at 39 weeks of gestation, and
weighed 6Ib 2oz at birth. His mother had hypoglycemic episodes and
complained of decreased fetal movements during pregnancy. He had
a positive maternal family history of Congenital Fiber Type
Disproportion (CFTD) and Nemaline Myopathy (NM). He had a
positive paternal family history of Depression and Type 1 Diabetes
Mellitus (DM). His four half siblings and one full brother were
unaffected. Serum Creatine Kinase (CK) and Electromyography
(EMG) findings are not available. A left lateral thigh muscle biopsy
was performed. Describe the microscopic findings on the H&E and
histochemical slides?
Click here to view the slides.
Answer
H&E section shows increased myofiber size variability with some
internalized nuclei and many fibers with central clearing (vacuoles). No
degenerating or regenerating fibers are identified. Some hyaline fibers are
seen. Multifocal perivascular and perimysial mononuclear inflammatory
infiltrates are present.
Gomori trichrome section is negative for ragged red fibers, rimmed
vacuoles, or definite nemaline rods.
NADH-TR section shows central clearing without central cores.
Oil red O and PAS sections show no abnormal accumulations of lipid and
glycogen material, respectively. The central clearing (vacuoles) do not
react with PAS. Some fibers show centrally prominent PAS reactivity.
Answer
ATPase sections show a normal checkerboard pattern with
a Type 1 to Type 2 fiber ratio of 2:1.
Esterase section shows increased reactivity in hyaline
fibers only.
Succinic dehydrogenase (SDH) section shows no SDH-rich
fibers.
Cytochrome oxidase (COX) section shows no COXnegative fibers.
Question 2
What additional immunostains would you need to rule out
other important differential diagnoses and confirm the final
diagnosis in this case?
Answer
Merosin should be performed for possible merosindeficient congential muscular dystrophy especially it the
creatine kinase is elevated. Immunostains for other
dystrophies could be performed but are less likely to
present with neonatal hypotonia. In this case,
immunostains for Dystrophin 1 (mid-rod), Dystrophin 2
(carboxy terminus), Merosin, Adhalin (alpha-sarcoglycan),
and Dysferlin were performed.
Question 3
What do you see on this Dystrophin 1 (mid-rod)
immunostain slide?
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Answer
Dystrophin 1 (mid-rod) section show normal sarcolemmal
labelling of all fibers.
Question 4
What do you see on this Dystrophin 2 (carboxy terminus)
immunostain slide?
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Answer
Dystrophin 2 (carboxy terminus) section show normal
sarcolemmal labelling of all fibers.
Question 5
What do you see on this Merosin immunostain slide?
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Answer
Merosin section show normal subsarcolemmal labelling of
all fibers.
Question 6
What do you see on this Adhalin (alpha-sarcoglycan)
immunostain slide?
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Answer
Adhalin (alpha-sarcoglycan) section show normal
subsarcolemmal labelling of all fibers.
Question 7
What do you see on this Dysferlin immunostain slide?
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Answer
Dysferlin section show normal subsarcolemmal labelling
of all fibers, with occasional cytoplasmic reactivity.
Question 8
What is your final diagnosis in this case?
Answer
Centronuclear Myopathy
The inflammation is a non-specific finding in this case.
Question 9
What is the mode of inheritance of the severe neonatal,
often fatal, form of centronuclear myopathy (myotubular
myopathy)?
A.Autosomal Recessive
B.Autosomal Dominant
C.X-linked Recessive
D.X-linked Dominant
Answer
C. X-linked Recessive