What are NAGA-related Disorders? NAGA-related disorders, also known as Schindler disease, are inherited lysosomal storage disorders caused by harmful genetic changes (variants) in the NAGA gene. Individuals with NAGA-related disorders are unable to break down substances known as glycoproteins and glycolipids. In individuals with NAGA-related disorders, the buildup of glycoproteins and glycolipids in the lysosomes causes cell damage in the nervous system and other parts of the body, leading to primarily neurological symptoms. There are three subtypes of NAGA-related disorders and symptoms ranging from mild to severe, even within the same family. Schindler disease type I Schindler disease type I, also called infantile type, is the most severe form. Infants may appear healthy at birth, with symptoms usually developing within the first year of life. Infants may experience developmental delay and lose skills they have already gained. Additional symptoms may include weakness, low muscle tone (hypotonia), blindness, and seizures. Schindler disease type II Schindler disease type II, also called Kanzaki disease, typically has milder symptoms that develop after puberty. Symptoms may include mild developmental delay, hearing loss, weakness and loss of sensation, and pain crises. A distinguishing physical trait for individuals with Schindler disease type II is the presence of hard bumps on the skin (angiokeratomas) caused by enlarged blood vessels. Individuals may also have distinct facial features. Schindler disease type III The severity of Schindler disease type III lies between that of types I and II. The age of onset for symptoms may range between infancy and early childhood. Symptoms of type III may include developmental delay, seizures, enlarged liver (hepatomegaly), weakened and enlarged heart (cardiomyopathy), and features of autism spectrum disorders. How common are NAGA-related Disorders? The exact incidence of NAGA-related disorders is unknown. Only a few individuals have been diagnosed with each type of disorder worldwide. How are NAGA-related Disorders treated? There is no cure for NAGA-related disorders. Treatment is directed at managing an individual's specific symptoms and may include medications to help control seizures and ensuring proper nutrition and hydration. Some individuals may need physical or speech therapy or interventions for developmental delay. What is the prognosis for an individual with NAGA-related Disorders? The prognosis depends on which subtype of the condition an individual has. For individuals with Schindler disease type I, symptoms typically begin in the first year of life, and many do not survive past childhood. Individuals with Schindler disease type II will often have a later onset, with symptoms first appearing after puberty; the few individuals with this type of disease can live a relatively normal life. Schindler disease type III can present with varying ages of onset for symptoms, ranging from infancy to adulthood. The prognosis depends on the individual's symptoms. Other names forNAGA-related disorders Alpha-NAGA deficiency Alpha-galactosidase B deficiency GALB deficiency Kanzaki disease NAGA deficiency Schindler disease References Clark, et al., 2009, J Mol Biol., 393(2):435-47, PMID: 19683538 Desnick, et al., 1990, J Inherit Metab Dis, 13(4):549-59, PMID: 2122121 Gregg, et al., 2021, Genet Med, 23(10):1793-1806, PMID: 34285390 Mohamed, et al., 2020, J Mol Neurosci., 70(1):45-55, PMID: 31468281 OMIM: Online Mendelian Inheritance in Man, OMIM [609241], 2016, https://www.omim.org/entry/609241 Wolfe, et al., 1995, J Neurol Sci, 132(1):44-56, PMID: 8523030