What are the other Names for this Condition? (Also known as/Synonyms)

• HAL Deficiency
• Histidase Deficiency
• Histidinuria

What is Histidinemia? (Definition/Background Information)

• Amino acids are complex organic compounds of biological significance. They are responsible for protein production in the human body, which is necessary to sustain life; for this reason amino acids are called the building blocks of proteins. One such amino acid is histidine
• When the levels of histidine in blood increases, the condition is known as Histidinemia. It is an inherited genetic disorder caused by mutation in the HAL gene
• Histidinemia, generally, is of no clinical (health) significance and the disorder is asymptomatic in most affected individuals
• However, it can lead to neurological symptoms, if there is a medical issue affecting the newborn baby, during or immediately following delivery. The complications for the infant can include intellectual impairment and severe growth retardation in some cases
• In such cases, Histidinemia requires to be treated and the medical management of the disorder may include dietary regulation and enzyme replacement. Children with developmental delays may need special therapy and lifelong support
• The prognosis of Histidinemia is very good for a majority of individuals; only about 1 in 10 cases require medical assistance and supportive therapy

Who gets Histidinemia? (Age and Sex Distribution)

• Histidinemia is an uncommon, inherited disorder that is present at birth
• Both male and female genders are equally affected
• The prevalence rate varies widely among the global population, from 1 in 8000 to 1 in 180,000
• The incidence of the disorder is observed higher in Japan and Quebec (1 in 8000-9000) for some unknown reason. However, all racial and ethnic groups may be affected

What are the Risk Factors for Histidinemia? (Predisposing Factors)

• Histidinemia is transmitted genetically from the parents to their offspring; hence those with a family history of Histidinemia, are at high risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Histidinemia? (Etiology)

• Histidinemia is a genetic disorder that is inherited in an autosomal recessive pattern
• In this disorder, there are genetic mutations in the HAL gene, which is responsible for the production of the histidase enzyme
• Due to the mutation, the enzyme functions abnormally and causes the buildup of histidine in blood, urine, and cerebrospinal fluid. However, this does not trigger any adverse health outcomes in the body, in most cases

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Histidinemia?

Most individuals with Histidinemia may not be aware that they have this disorder, because it is a benign condition that does not cause any significant signs and symptoms (in over 90% of the individuals). On the other hand, the occurrence of any complication (such as a lack of oxygen) during the neonatal period or childbirth can make the newborn vulnerable to the following health conditions:

• Learning disorders
• Behavioral disorders
• Intellectual impairment

How is Histidinemia Diagnosed?

Diagnostic tests that are performed for Histidinemia may include:

• Complete physical exam with evaluation of medical history
• Screening of the newborn baby having a family history the disorder, which is very important
• Neurological study and evaluation
• Testing of cerebrospinal fluid, blood, and urine samples
• Genetic tests and analysis to detect mutations
• Prenatal exams include amniocentesis and chorionic villus sampling to check for mutation on the HAL gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Histidinemia?

Complications due to Histidinemia usually occur if other medical disorders coincidentally affect the infant during or immediately following birth. These include:

• Severe mental retardation
• Learning or speech disability
• Growth delays

How is Histidinemia Treated?

In over 90% of the cases, individuals with Histidinemia require no treatment. For the individuals whose condition needs to be managed, the following methods are generally employed:

• Low-histidine level diet
• Enzyme replacement therapy
• Children with developmental delays are treated based on individual assessment and missed growth milestones. In order to improve motor skills and mental disabilities, special therapeutic treatment (by speech, physical, and occupational therapists) and supportive care is provided

How can Histidinemia be Prevented?

• Currently, there are no specific methods or guidelines to prevent Histidinemia, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Histidinemia
• It is essential that expectant mothers be regularly screened during the course of pregnancy. Also, after delivery of the child, a proper neonatal screening program is recommended

What is the Prognosis of Histidinemia? (Outcomes/Resolutions)

• A significant majority of the individuals need no treatment for Histidinemia and they are able to lead a healthy normal life
• A very small percentage of individuals require management of the condition, which may not be too difficult, since Histidinemia is typically a benign condition
• However, complications secondary to medical conditions that develop in the infant around the time of birth may require symptomatic treatment and therapy

Additional and Relevant Useful Information for Histidinemia:

The medical community has many unresolved questions on Histidinemia that includes the role of histidase, molecular characteristics, treatment mode, etc.