Infantile neuroaxonal dystrophy (INAD) is a rare inherited, progressive neurodegenerative disease.
In most cases, the infants with Infantile neuroaxonal dystrophy appear to grow normally until at about 6-18 months of age, when the symptoms start appearing. Infants may experience delay in achieving psychomotor development. Infantile neuroaxonal dystrophy may be classical or atypical.
Classical Infantile neuroaxonal dystrophy presents between 6 months to 3 years with psychomotor delay and developmental regression. It is characterized by truncal hypotonia progressing to tetraparesis. Dementia is also seen. Visual signs include strabismus, pendular nystagmus, uncoordinated eye movement, optic atrophy and failing vision. Seizure episodes may be seen.
The progression of disease is usually rapid. Many affected children never learn to walk or lose this ability shortly after attaining it. During the end stages of disease, severe spasticity, progressive cognitive decline, and visual impairment result in a vegetative state . Death occurs as a result of secondary illnesses such as aspiration pneumonia, associated with bulbar dysfunction. Many affected children do not survive beyond their first decade, but some survive into their teens or later.
Onset of atypical neuroaxonal dystrophy can be seen in early childhood or in late teens. Speech delay and neurobehavioral disturbance is seen. Progressive dystonia and dysarthia is seen. Visual disturbances are same as seen in classical neuroaxonal dystrophy like nystagmus, squints and gradually optic atrophy and ultimately loss of vision. Tetraparesis occurs late in disease.
Neuropsychiatric disturbance include impulsivity, poor attention span, hyperactivity, and emotional liability. The disease progresses same like classical Infantile neuroaxonal dystrophy, leaving the child dependant .
Workup should include a thorough neurological examination, a complete ophthalmic check up and a correct genetic consultation. A proper history should be taken to know the course of disease and time of onset. The age of the child should be considered. It along with the subjective and objective symptoms of the patient helps to come near the diagnosis.
The treatment of Infantile neuroaxonal dystrophy remains palliative to provide symptomatic relief to the patient. Every care should be taken to control the symptoms and give comfort to the child.
Pharmacologic treatment is given to control seizure and spasticity. Trial of oral or intrathecal baclofen is recommended for those having significant dystonia. Psychiatrists are brought in for the later stage when the patient has neuropsychiatric symptoms. Fiber supplements are given to treat constipation which is likely to be caused due to immobility. Gastric feeding tube or tracheostomy is done to prevent aspiration pneumonia.
Transdermal scopolamine patch to reduce the secretion in those with excessive drooling. Drugs to treat pain and infection are given if required. A physiotherapist can be engaged to guide and assist parents on positioning their affected children to provide better comfort. Specialized schooling is required. Some of the alternative therapies like cranial osteopathy and massage are found to give symptomatic relief.
There are no symptoms at birth, however as the child grows from 6 months to 2 years, the symptoms become apparent. The condition worsens with age. Over several years, the child becomes dependant wholly and eventually loses all learned skills and intellect. Death occurs by the age of 5-10 years. The prognosis is thus poor.
Infantile neuroaxonal dystrophy is caused by deposition of a substance called spheroid bodies (because of their appearance under microscope) in the axons of the nerves particularly those going to the muscles, skin and conjunctiva. It is not clear why these substances are deposited, but it is thought that the gene responsible for clearing the unwanted substance does not function properly.
Mutations in PLA2G6 gene are identified as the cause of the disease. However, some other gene is also thought to be responsible for it. Research for this is under progress  . In some cases there is no mutation found and the cause remains a complete mystery.
It is a rare disease with the incidence of less than 1: 200,000. No gender or race predilection has been found owing to the exceedingly low number of cases.
PLA2G6 is the gene which has the instruction for making A2 phospholipase. It is involved in metabolism of phospholipids. Phospholipid metabolism is important to keep the cell membrane intact and function properly. A2 phospholipase produced from PLA2G6, regulates the level of phosphatidycholine which is found abundantly in cell membranes. Mutation in the PLA2G6 gene causes impairment in functioning of the enzyme and thus causes disturbance in maintaining the integrity of cell membrane leading to development of spheroid bodies in the nerve axon .
Due to the formation of such abnormal depositions in the parts of the brain, their function is hampered. The nerve endings going to different parts of body are affected due to presence of spheroid bodies particularly those going to muscles, skin and conjunctiva, thus gradually declining their function. It is also believed that there are abnormal amounts of iron deposited in the basal ganglia of the brain too   .
Infantile neuroaxonal dystrophy is an inherited disorder and thus genetic counseling is done to determine the couple at risk of having affected child. Prenatal testing for Infantile neuroaxonal dystrophy is now usually possible if PLA2G6 gene is found in affected child.
Infantile neuroaxonal dystrophy (INAD) is a rare, hereditary disorder affecting the nervous system. It is seen in children between the ages of 6-18 months were they experience delay in acquiring motor and intellectual skills, have progressive loss of vision and reduction of physical and mental performance. It is also observed in late teenage when it is called atypical neuroaxonal dystrophy. In both the cases, the disease progresses towards death and symptomatic relief is the only treatment available.
It is an autosomal recessive disorder wherein both the parents are carrier of the disease and there are 25% chances of one of their kid having the disease. In the 1950’s, Dr Seitelberger described the disorder and it is still sometimes known as Seitelberger’s disease .
Infantile neuroaxonal dystrophy (INAD) is a rare inherited disease whereby both the parents are carrier and thus the chances of one of their child having Infantile neuroaxonal dystrophy is 25%. It is seen between the age of 6-18 months or it can also occur in late teenage.
The nerve endings responsible for carrying message to other parts of body are affected causing a progressive loss of vision and of physical and mental skills. Their muscles become weak and floppy and gradually very stiff. Eventually affected children loose their ability to move independently. Muscle strength decreases causing them difficulty in taking feeds and breathing thus making them prone to various infections causing pneumonia. Seizure may also occur in some patient. Eyes are affected causing rapid, involuntary eye movement, eyes that look in same direction and gradually loss of vision. Hearing loss may also occur. Children with this disorder loose their memory and eventually loose awareness of their surroundings.
The disease progresses rapidly and the child usually does not cross the decade. Diagnosis is done by doing MRI of brain, ophthalmic examination and genetic counseling. Management includes symptomatic relief.