Alpha-N-acetylgalactosaminidase deficiency

Alpha-N-acetylgalactosaminidase deficiency, also known as Schindler disease, is an inherited disorder that can affect the development of the nervous system. People with alpha-N-acetylgalactosaminidase deficiency often have distinctive facial features that can be described as "coarse" and tooth abnormalities such as widely-spaced teeth and missing teeth (hypodontia).

The three types of alpha-N-acetylgalactosaminidase deficiency differ in the severity of their signs and symptoms and the age at which they first appear. The signs and symptoms of alpha-N-acetylgalactosaminidase deficiency can vary, even among members of the same family. 

Type I is the most severe form of this condition. Babies with alpha-N-acetylgalactosaminidase deficiency type I appear healthy at birth. However, by late infancy, these babies typically have trouble meeting normal developmental milestones. By the age of 2 years, individuals with type I begin to lose skills that they had already acquired (developmental regression). Individuals with type I often experience weak muscle tone (hypotonia), vision and hearing loss, and seizures. During early childhood, children with type I typically lose awareness of their surroundings and eventually become unresponsive.

Alpha-N-acetylgalactosaminidase deficiency type II is the least severe form. Type II is typically diagnosed in adulthood. Affected individuals may have mild cognitive impairment and hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). They may also experience a loss of sensation or muscle weakness in the extremities (peripheral neuropathy). Clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) are a characteristic feature of alpha-N-acetylgalactosaminidase deficiency type II.

Type III is the intermediate form of alpha-N-acetylgalactosaminidase deficiency. People with type III may show a variety of signs and symptoms, including developmental, speech, and language delays; seizures that begin in infancy; and features of autism spectrum disorder that appear in childhood. Autism spectrum disorder is characterized by impaired communication and socialization skills. People with type III may also have skeletal signs and symptoms, such as pain in the lower back, hips, and knees. Wear on the cartilage (disks) and bones of the neck (cervical spondylosis) and a cyst-like collection of cerebrospinal fluid that forms in the spinal cord (syringohydromyelia) have also been reported.