Phenotype_GenotypePhenotype/Genotype

There is a genotype/phenotype relationship in GAN. This means, depending on the type of mutation a GAN patient has on each copy of their GAN gene, and where each mutation is located on the gene, this can determine how quickly they will progress, and what symptoms will appear first. For example, in two subjects that I would categorize as having typical GAN, one may not have severe problems swallowing until the age of 20, while the other requires a g-tube at the age of 13. Also,two siblings in FL who have the identical GAN mutation, seemed to progress at different rates. One brother met all milestones about 2 years before the other (walker, wheelchair, g-tube placement etc.). Also, it has been reported that mutations at the beginning of the gene, (the domain region) tend to progress more quickly than those whose mutations are at the end of the gene (the Kelch region).

In milder cases of GAN, the only symptoms reported are neuropathy (foot drop, loss of sensation and strength in the legs and feet, and sensory ataxia (trouble balancing, especially with eyes closed).

This is an example of typical/severe GAN:

Case Reports:

Mild GAN – case report from a parent:

(Nadia will give Kelly the details.)

Typical GAN – case report from a parent:

Baby – dairy sensitivity present after weaning from breast milk; met all development milestones

Age of 2.5 – left arched seemed to begin rolling inward when she would round a corner.

Age 3 – awkward gait and trouble balancing

Age 5 – infrequent bowel movements – ½ cap of Miralax daily keeps regularity

Age of 6 – noticeable eye nystagmus – eyes twitch left to right quickly, involuntarily

Age 6.5 – began using a walker at school; cannot walk across a room without holding on to something; Received an A+ on pulmonary (lung) function test.

Age 7.5 – public hair began growing; began sleep apnea and snoring (hasn’t had a sleep study performed yet, but needs one); You can hear the vocal cords flap when taking a deep breath.  It sounds like congestion, but realized it’s very likely the start of vocal paresis, and the sounds is likely the vocal cords flapping and starting to obstruct the airway.

8th Birthday status – cognition is intact and smart as a whip!  No swallowing problems. Needs the walker full-time, but still doesn’t use it at home.  We have an adaptive umbrella stroller, but we only use it in shopping malls.  Exercise is the best thing for these kids.  The two older, slower progressing patients emphasize that exercise helps them keep function longer.  A 19 year old in New Zealand said, “Do not sit still for a minute.  Once you lose function, it’s nearly impossible to regain it”.

Since the age of 5, we’ve been using specific frequency microcurrent.  We have an at-home unit that has frequencies pre-programmed for: Protein overload, legs; Muscle strength; Inflammation; Full Brian; Cerebellum function; GI function.  Mostly, we use the leg frequencies and we feel this has helped with silent inflammation.  Twice a day, I stretch the achilles tendons, which are very right due to collapsed arches.  I also do toe grip exercises by placing a finger, lengthwise under the toes and I ask her to squeeze my finger.  Toe grip strength is significantly better after having used the specific frequency microcurrent machine.

We also have our daughter on high quality supplements.  Twice a year, we pay out of pocket for an Individual Optimal Nutrition (ION) Panel and Amino Acid panel of blood and urine.  The naturopathy prescribes supplements based on the results of these panels.  We have no idea if the supplements help or not.  Since many neurotransmitters are made it the gut, we figure striving for optimal nutrition through supplements can’t hurt.