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

• Dibasic Aminoaciduria 2
• Hyperdibasic Aminoaciduria Type 2
• Lysinuric Protein Intolerance

What is Dibasic Aminoaciduria Type 2? (Definition/Background Information)

• Dibasic Aminoaciduria Type 2, also known as lysinuric protein intolerance (LPI), is a very rare inherited multisystem condition caused by disturbance in amino acid metabolism. It is mainly found in Italy and Finland where prevalence is 1/60,000
• The metabolic disturbance in Dibasic Aminoaciduria Type 2 causes increased renal excretion and reduced absorption from intestine of cationic amino acids, and orotic aciduria
• Patients affected by Dibasic Aminoaciduria Type 2 may present with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, bone marrow abnormalities, osteopenia, episodes of hyperammoniaemic coma, mental retardation, altered immune response, chronic renal disease, and lung involvement (mostly pulmonary alveolar proteinosis - PAP - and, to a lesser extent, interstitial lung disease)
• Dibasic Aminoaciduria Type 2 is caused by mutations of solute carrier family 7A member 7 (SLC7A7) located at chromosome 14q11.2
• Diagnosis requires amino acid assays in plasma and urine where increased urinary excretion and low plasma concentration of lysine, arginine, and ornithine indicate positive diagnosis
• Treatment revolves around protein-restricted diet and supplement of lysine, ornithine, and citrulline. The complication of pulmonary alveolar proteinosis has been reported to be successfully treated by whole lung lavage
• Prognosis varies depending on pulmonary complications. Pulmonary involvement represents a major cause of impaired clinical course and fatal outcome

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Dibasic Aminoaciduria Type 2? (Age and Sex Distribution)

• Dibasic Aminoaciduria Type 2 is a rare congenital disorder, mainly found in Italy and Finland where prevalence is 1/60,000
• Disease manifestation can begin in the neonatal period or infancy
• Both males and females may be affected

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

What are the Risk Factors for Dibasic Aminoaciduria Type 2? (Predisposing Factors)

• A positive family history may be an important risk factor, since Dibasic Aminoaciduria Type 2 can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Dibasic Aminoaciduria Type 2? (Etiology)

• Dibasic Aminoaciduria Type 2 is caused by mutations of solute carrier family 7A member 7 (SLC7A7) located at chromosome 14q11.2
• The mutation leads to defective cationic amino acid transport at the basolateral membrane of epithelial cells in the kidney and intestine
• Dibasic Aminoaciduria Type 2 may be inherited in an autosomal recessive manner

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

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 Dibasic Aminoaciduria Type 2?

The signs and symptoms of Dibasic Aminoaciduria Type 2 may include:

• Vomiting
• Diarrhea
• Failure to thrive
• Hepatosplenomegaly
• Bone marrow abnormalities
• Osteopenia
• Episodes of hyperammoniaemic coma
• Mental retardation
• Altered immune response
• Chronic renal disease
• Pulmonary alveolar proteinosis (PAP)
• Interstitial lung disease

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Dibasic Aminoaciduria Type 2 Diagnosed?

Dibasic Aminoaciduria Type 2 is diagnosed on the basis of the following information:

• Amino acid assays in plasma and urine where increased urinary excretion and low plasma concentration of lysine, arginine, and ornithine indicate positive diagnosis

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Imaging tests
• Biopsy studies, if necessary

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 Dibasic Aminoaciduria Type 2?

The complications of Dibasic Aminoaciduria Type 2 may include:

• Malnourishment
• Pulmonary alveolar proteinosis that may lead to the following conditions:
• Lung infections
• Lung fibrosis
• Cor pulmonale (right-side heart failure)

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Dibasic Aminoaciduria Type 2 Treated?

• The treatment for Dibasic Aminoaciduria Type 2 revolves around protein-restricted diet and supplement of lysine, ornithine, and citrulline
• The complication of pulmonary alveolar proteinosis has been reported to be successfully treated by whole lung lavage

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Dibasic Aminoaciduria Type 2 be Prevented?

Dibasic Aminoaciduria Type 2 may not be preventable, since it is a genetic disorder.

• 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

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Dibasic Aminoaciduria Type 2? (Outcomes/Resolutions) 

• The prognosis of Dibasic Aminoaciduria Type 2 varies depending on pulmonary complications
• Pulmonary involvement represents a major cause of impaired clinical course and fatal outcome 

(Source: Lysinuric Protein Intolerance; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Dibasic Aminoaciduria Type 2:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/

http://www.dovemed.com/diseases-conditions/pulmonary-alveolar-proteinosis/