Histidinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of the enzyme histidase. Histidase is needed for the metabolism of the amino acid histidine. Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder, leading to a reduction in the prevalence of neonatal screening procedures. Presentation
Histidinemia is considered benign as most patients remain asymptomatic, early correlational evidence from the first decade of histidinemia research lead to the theory that histidinemia was associated with multiple developmental symptoms including hyperactivity, speech impediment, developmental delay, learning difficulties, and sometimes mental retardation. However, these claims were later deemed coincidental as a large subpopulation of infants that tested positive for histidinemia were found to have normal IQ and speech characteristics; as such histidinemia has since been reclassified as a benign inborn error of metabolism. Molecular mechanism
Histidinemia occurs as the result of an inborn error of metabolism that may result in either an inactive or a severely reduced histidine ammonia-lyase (HAL) enzyme activity. The gene that encodes for HAL spans a roughly 25 kb and consists of 21 exons located at the 12q22-q24.1 position of human chromosome 12. There are eight mutations currently associated with autosomal recessive histidinemia, that include: four missense mutations, two exonic polymorphisms and two intronic polymorphisms. Diagnosis
Histidenemia is characterized by increased levels of histidine, histamine and imidazole in blood, urine and cerebrospinal fluid. This also results in decreased levels of the metabolite urocanic acid in blood, urine, and skin cells.
Skew deviation is an unusual ocular deviation (strabismus), wherein the eyes move upward (hypertropia) in opposite directions. Skew deviation is caused by abnormal prenuclear vestibular input to the ocular motor nuclei, most commonly due to brainstem or cerebellar stroke. Other causes include multiple sclerosis and head trauma. Skew deviation is usually characterized by torticollis (head tilting) and binocular torsion. The exact pathophysiology of skew deviation remains incompletely understood. Skew deviation appears to be a perturbation of the ocular tilt reaction, which is itself is most likely a vestigial righting response used to keep fish and other lateral-eyed animals properly oriented.There are three types of skew deviations:Type 1: Upward deviation of both eyes; sound-induced vestibular symptoms; both eyes show counterclockwise rotary upward rotation
Type 2: Hypertropia in one eye; dorsolateral medullary infarctions; excyclotropia in the ipsilateral eye; hypertropia in the contralateral eye
Type 3: Simultaneous hypertropia one eye and hypotropia in the other eye; upper brainstem lesion

References
Further reading
Adams, Raymond D.; Victor, Maurice; Ropper, Allan H. (1997). Principles of Neurology (6 ed.). New York: McGraw Hill, Health Professions Division. ISBN 978-0-07-067439-4.