What is Infantile Neuroaxonal Dystrophy?
Infantile Neuroaxonal Dystrophy (INAD) is a rare genetic neurodegenerative disorder that affects children. It is part of a group of neurodegenerative diseases called phospholipase associated neurodegeneration (PLAN) that fall under a larger umbrella of NBIAs (neurodegenerative brain iron accumulation) [5]. INAD causes neurological regression and results in the loss of motor control and cognitive abilities. It ultimately results in death about 10 years after diagnosis [3].
Inheritance and Prevalence
Infantile neuroaxonal dystrophy is an autosomal recessive disorder. This means that for an individual to have INAD they must receive a mutant copy of the gene involved from both their mother and their father. PLA2G6 is located on chromosome 22 which is an autosome. The sex chromosomes are not involved so the prevalence of INAD is equal in males and females [4]. INAD is a very rare disorder and the exact prevalence of it within the population is not known. The prevalence of PLA2G-associated neurodegeneration (PLAN) is about 1 in 1,000,000 within the population [3]. This estimate however includes atypical neuroaxonal dystrophy and dystonia-parkinsonism in addition to infantile neuroaxonal dystrophy.
Symptoms and Diagnosis
INAD is a progressive neurological disorder. The symptoms generally arise between the ages of 6 months and 2 years and gradually get worse over time [5]. For the first 6 months to two year of their lives individuals with INAD seem to develop normally and can hit milestones like smiling, sitting up, laughing and others. However once onset occurs these skills are lost. Many children with INAD never learn to walk. If they do learn to walk the ability is lost very soon after learning. One of the first symptoms that is generally noticed is ataxia (loss of muscle control) [4]. Having crossed eyes is another common symptom that is generally seen early on and eventually optic atrophy occurs. Some individuals with INAD may develop seizures later in their disease progression [4]. Overall, the progression of the disease is quite rapid, and many children do not live past 10 years old [4].
If INAD is suspected based on an individual’s symptoms there are several different types of tests that can be done to confirm the diagnosis. The most straightforward form of diagnosis is using a genetic test to look for a possible mutation in the PLA2G6 gene. They can also take biopsies of nerve tissue or use an MRI. In addition to confirming whether an individual has INAD, nerve tissue biopsies and MRIs are helpful because they can help to determine the progression of the disease [3]. |
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Role of PLA2G6 in INAD
Infantile neuroaxonal dystrophy is a subset of PLAG6-associated neurodegeneration called phospholipase associated neurodegeneration (PLAN) since it is caused by a mutation in the PLA2G6 gene [4]. Mutations in PLA2G6 impact the functionality of the enzyme A2 phospholipase preventing it from properly breaking down lipids [3]. The inability to breakdown lipids results in a disruption of cell membrane maintenance, the development of spheroid bodies on axons and the buildup of iron in the brain [2,3]. PLA2G6 mutations are also associated with other neurological disorders such as atypical neuroaxonal dystrophy and dystonia-parkinsonism which have a much later onset than INAD [2]. Collectively INAD, atypical neuroaxonal dystrophy and dystonia-parkinsonism make up PLAN. |
Notable Organizations and Resources
There are several notable organizations that are committed to providing families impacted by INAD with resources as well as searching for treatments and a cure. They have lots of good information about the disease. In addition to learning about the specifics of the disease it is important to understand what life is actually like for those directly impacted by INAD. Whitney Frost whose video on disease regression is linked above has a TikTok that is a great way to gain a better understanding of the day to day life of those impacted by INAD.
References1: All disorders. (n.d.). Retrieved May 06, 2021, from https://www.ninds.nih.gov/Disorders/All-Disorders/Infantile-Neuroaxonal-Dystrophy-Information-
2: PLA2G6 gene: MedlinePlus Genetics. (2020, August 18). Retrieved May 06, 2021, from https://medlineplus.gov/genetics/gene/pla2g6/#:~:text=The%20PLA2G6%20gene%20provides%20instructions,integrity%20of%20the%20cell%20membrane. 3: Infantile Neuroaxonal Dystrophy (INAD). (n.d.). Retrieved May 06, 2021, from https://www.raregenomics.org/infantile-neuroaxonal-dystrophy-inad 4: NBIA. (n.d.). Retrieved May 06, 2021, from http://nbiacure.org/learn/nbia-disorders/plan/inad/ 5: What is INAD? (n.d.). Retrieved May 06, 2021, from https://www.inadcure.org/about-us/what-is-inad/ Header Photo: https://www.york.ac.uk/study/undergraduate/courses/bsc-genetics/ |
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