Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study.
BACKGROUND
Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as alpha-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM.


METHODS
We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 micromol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals.


RESULTS
For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for alpha-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting.


CONCLUSIONS
The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.
Sparks
Susan
S
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. ssparks@mail.nih.gov <ssparks@mail.nih.gov>
Rakocevic
Goran
G
Joe
Galen
G
Manoli
Irini
I
Shrader
Joseph
J
Harris-Love
Michael
M
Sonies
Barbara
B
Ciccone
Carla
C
Dorward
Heidi
H
Krasnewich
Donna
D
Huizing
Marjan
M
Dalakas
Marinos C
MC
Gahl
William A
WA
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D018979:Myositis, Inclusion Body / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy*; D010865:Pilot Projects; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous