Neurodegeneration with Brain Iron Accumulation 2a (NBIA2A)

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MedlinePlus Genetics: ⁴² Infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills (developmental regression). In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. They generally have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding. Muscle weakness can also result in breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the nerve that carries information from the eye to the brain (the optic nerve) often occur in infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and they eventually lose awareness of their surroundings.Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. The relationship of these features to the symptoms of infantile neuroaxonal dystrophy is unknown.

MalaCards based summary: Neurodegeneration with Brain Iron Accumulation 2a, also known as infantile neuroaxonal dystrophy, is related to dementia, lewy body and parkinson disease 3, autosomal dominant, and has symptoms including ataxia, dysdiadochokinesis and gait ataxia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 2a is PLA2G6 (Phospholipase A2 Group VI), and among its related pathways/superpathways are Metabolism and Glycerophospholipid biosynthesis. The drugs Desipramine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and skin, and related phenotypes are developmental regression and cerebellar atrophy

NINDS: ⁵² Infantile neuroaxonal dystrophy (INAD) is a rare inherited neurological disorder. It affects axons, the part of a nerve cell that carries messages from the brain to other parts of the body, and causes progressive loss of vision, muscular control, and mental skills. Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. While the basic genetic and metabolic causes are unknown, INAD is the result of an abnormal build-up of toxic substances in nerves that communicate with muscles, skin, and the conjunctive tissue around the eyes.  Symptoms usually begin within the first 2 years of life, with the loss of head control and the ability to sit, crawl, or walk, accompanied by deterioration in vision and speech.  Some children may have seizures.  Distinctive facial deformities may be present at birth, including a prominent forehead, crossed eyes, an unusually small nose or jaw, and large, low-set ears.  INAD is an autosomal recessive disorder, which means that both parents must be carriers of the defective gene that causes INAD to pass it on to their child. Electrophysiology (nerve conduction velocities) may be helpful for diagnosis, although diagnosis is usually confirmed by tissue biopsy of skin, rectum, nerve or conjunctive tissue to confirm the presence of characteristic swellings (spheroid bodies) in the nerve axons.

Orphanet: ⁵⁸ Infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy (INAD/atypical NAD) is a type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two.

OMIM®: ⁵⁷ Neurodegeneration with brain iron accumulation-2A is an autosomal recessive neurodegenerative disease characterized by onset in the first 2 years of life; it is also referred to as infantile neuroaxonal dystrophy (INAD). Pathologic findings include axonal swelling and spheroid bodies in the central nervous system (review by Gregory et al., 2009). (256600) (Updated 08-Dec-2022)

GARD: ¹⁹ Infantile neuroaxonal dystrophy is a type of lipid storage disorder that mostly affects the nervous system. It has two forms, a classic form and an atypical form. Infantile neuroaxonal dystrophy is caused by changes (pathogenic variants) in the PLA2G6 gene and is inherited in an autosomal recessive pattern.

Disease Ontology: ¹¹ A neurodegeneration with brain iron accumulation that has material basis in autosomal recessive inheritance of mutation in the PLA2G6 gene on chromosome 22q13.1 and is characterized by onset in the first 2 years of life.

UniProtKB/Swiss-Prot: ⁷³ A neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years.

Wikipedia: ⁷⁵ Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the... more...

Clinical features from OMIM®:

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