Carrier rate in Iranian Jews:
Approximately 1 in 12 to 1 in 15

Carrier rate in the general population:
Rare

Other ethnic groups in which it occurs:
Japanese (higher frequency); all other ethnic groups (lower frequency)

Age of onset of symptoms:
In many cases, 20-30 years of age. As young as 17 and as old as 52 years of age have been known to be affected.

Symptoms:
HIBM stands for Hereditary Inclusion Body Myopathy, a rare neuromuscular disorder which causes progressive muscle wasting in the arms and legs, but initially sparing the quadriceps muscles.  Some early signs include frequent loss of balance, weakness of muscles causing difficulty to walk on the heels or run and a weak index finger. Weakness and severity may vary from person to person. In some the weakness begins in the legs while in a minority of cases weakness begins in the hands. This disorder does not affect the brain, sensation or internal organs.

Average lifespan:
HIBM is not a life threatening disorder but can be debilitating and may cause lifelong severe disability. It can progress to marked disability within 10 15 years, confining many patients to the wheelchair. With early detection it may be possible to slow the progression of the disease with current treatment trials that are currently available.

What causes the features of the disease:
Mutations in a single gene that codes for a protein enzyme in the body required for the synthesis of sialic acid which is vital for normal muscle function. More specifically, the mutations are found in the GNE gene, coding for the enzyme, UDP-N-Acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, cause at least three disorders: HIBM, Nonaka myopathy, and a rare dominant inborn error of metabolism, sialuria (MIM: 269921). The enzyme is bifunctional and catalyzes the first two steps in the biosynthesis of sialic acid which is required for normal muscle function.

Treatment or management:
There are currently no proven cures or treatments for HIBM but researchers are currently testing various treatments for HIBM on a mouse model, including gene therapy, sialic acid replacement treatments, and stem cell based therapies. Clinical human trials of sialic acid replacement therapy is also underway with hopes of achieving positive results. Regular visits to a neuromuscular specialist in order to monitor the progression of the disorder are very important. Other available approaches to slow progression of the disorder and maintain good health include holistic approaches, healthy eating (e.g. organic and other diets), food supplements, physical therapy, maintaining a healthy spiritual/positive outlook, and living life to the fullest.

Carrier testing - number of mutations screened for and detection rate in the Iranian Jewish population:
The exon 12 p.Met712Thr mutation is the only GNE mutation identified to date among Middle Eastern and Iranian Jewish individuals. In Japanese patients, the p.Val572Leu mutation in exon 10 is the most common mutation although others are known.

Other testing information:
Tests that may be ordered to ascertain if an individual has HIBM (IBM2) include: Blood test for serum Creatine Kinase (CK or CPK); Nerve Conduction Study (NCS) / Electomyography (EMG); Muscle Biopsy; Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps; Blood Test or Buccal swab for genetic testing;.

Current research:
Researchers at Hadassah, USC, UCLA, UCSD, Johns Hopkins University, Canada, NIH, and Japan are contributing towards finding an effective treatment.

For more information:
Neuromuscular Disease Foundation:
   www.neuromuscdisease.org
HIBM Research Group:
   www.hibm.org
HIBM Israel:
   www.hibm.org.il
NIH HIBM Study:
   hibmstudy.nhgri.nih.gov
Ultragenyx:
   www.ultragenyx.com