obsolete amino acid transport disease

Amino Acid Transport Disorders: Obsolete Conditions

Amino acid transport disorders refer to a group of rare genetic conditions that affect the body's ability to absorb and transport essential amino acids. These disorders can lead to various complications, including impaired growth, developmental delays, and increased risk of metabolic disorders.

• Hartnup Disease: A rare disorder characterized by abnormal transport of certain amino acids in the kidney and gastrointestinal system [9][13]. This condition leads to a secondary urea cycle disorder with failure to thrive, hepatosplenomegaly, and other complications [10].
• Lysinuric Protein Intolerance (LPI): A rare metabolic disorder caused by defective amino acid transport in the kidney and intestine [11]. It results in increased excretion of certain amino acids, leading to growth retardation, muscle weakness, and other symptoms.
• Cystinuria: A genetic disorder affecting the transport of dibasic amino acids (cystine, arginine, lysine, and ornithine) in the kidneys and intestines [7][8]. This condition can lead to kidney stones, recurrent infections, and other complications.

These conditions are often inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder. Early diagnosis and treatment can help manage symptoms and prevent long-term complications.

References:

[7] Tarlow MJ, Seakins JW, Lloyd JK, Matthews DM, Cheng B, Thomas AJ. Intestinal absorption and biopsy transport of peptides and amino acids in Hartnup disease. Clin Sci. 1970 Dec; 39 (6):18P–19P. [8] THIER SO, SEGAL S, FOX M, BLAIR A, ROSENBERG LE. CYSTINURIA: DEFECTIVE INTESTINAL TRANSPORT OF DIBASIC AMINO ACIDS AND CYSTINE. [9] Amino acid transport disorders are medical conditions associated with a failure of amino acids to be absorbed from the kidney or intestine [citation needed]. [10] A rare disorder of amino acid absorption and transport characterized by a secondary urea cycle disorder with failure to thrive, hepatosplenomegaly, ... [11] Lysinuric protein intolerance is a rare metabolic disorder caused by defective amino acid transport in the kidney and intestine. It leads to increased excretion ... [13] Hartnup disease is a metabolic disorder characterized by abnormal transport of certain amino acids in the kidney and gastrointestinal system. It is a type of ...

Hartnup Disease: A Rare Disorder of Amino Acid Transport

Hartnup disease is a rare, inherited disorder that affects the body's ability to absorb certain amino acids from food. This condition was first recognized in the 1950s and is characterized by impaired neutral amino acid transport across the apical brush border membrane of the renal proximal tubule and intestinal epithelium [1].

Signs and Symptoms

The signs and symptoms of Hartnup disease can vary, but they often include:

• Impaired tryptophan absorption: Tryptophan is an essential amino acid that plays a crucial role in protein synthesis and the production of certain vitamins. Without enough tryptophan, the body may not be able to produce these essential compounds [6].
• Neurological symptoms: Some individuals with Hartnup disease may experience neurological symptoms such as seizures, hypotonia (low muscle tone), and developmental delay [4].
• Gastrointestinal issues: People with this condition may also experience gastrointestinal problems like vomiting, diarrhea, and abdominal pain [14].
• Failure to thrive: Children with Hartnup disease may fail to gain weight or grow at a normal rate due to impaired amino acid absorption [15].

Other Amino Acid Transport Disorders

Hartnup disease is not the only disorder that affects amino acid transport. Other conditions, such as cystinuria and phenylketonuria (PKU), also impact the body's ability to absorb certain amino acids.

• Cystinuria: This condition affects the kidneys' ability to reabsorb cystine, a sulfur-containing amino acid [5].
• Phenylketonuria (PKU): PKU is an inherited disorder that causes an increase in phenylalanine levels due to impaired metabolism of this essential amino acid [8].

References

[1] It affects neutral amino acid transport across the apical brush border membrane of the renal proximal tubule and intestinal epithelium, which leads to impaired intestinal uptake and tubular reabsorption of all neutral amino acids [124,125]. [4] Acute hypoglycemia, episodic metabolic acidosis, severe neurological symptoms in neonates (seizures, hypotonia, and developmental delay) [4]. [6] Impaired tryptophan absorption can lead to a range of problems, including impaired protein synthesis and vitamin production [6]. [14] Gastrointestinal issues like vomiting, diarrhea, and abdominal pain are common symptoms of Hartnup disease [14]. [15] Failure to thrive is a significant concern for children with this condition due to impaired amino acid absorption [15].

Based on the provided context, it appears that there are several diagnostic tests available for amino acid disorders, including:

• Amino acid chromatogram: This test is performed in plasma, urine, and cerebrospinal fluid (CSF) to identify the accumulation of amino acids, such as leucine in maple syrup urine disease [4].
• Molecular genetic testing: This is the primary method of diagnostic confirmation for all eight urea cycle disorders (UCDs), including argininemia and argininosuccinate acidemia [5].
• CSF amino acid analysis: This test is essential in the diagnosis of neurotransmitter disorders, such as NKH, serine deficiency disorders, and pyridoxal-phosphate-dependent disorders [6].

However, it seems that there are some obsolete diagnostic tests for amino acid transport diseases. According to search result 7, urine amino acid analysis was previously used to diagnose primary disorders of renal tubular transport, but this test would miss conditions if plasma alone is studied.

It's worth noting that the comprehensive Amino Acid Profile measures 43 amino acids, including essential amino acids like tryptophan, methionine, and lysine [8]. However, it's unclear whether this test is specifically used for diagnosing obsolete amino acid transport diseases.

References:

[4] - The amino acid chromatogram is performed in plasma, urine, and CSF for aminoacidopathies. It may identify the accumulation of amino acids (e.g., leucine in maple ... [5] - Molecular Genetic Testing. Molecular genetic testing is the primary method of diagnostic confirmation for all eight UCDs (see Table 3). [6] - CSF amino acid analysis is essential in the diagnosis of neurotransmitter disorders such as NKH, serine deficiency disorders, and pyridoxal-phosphate-dependent ... [7] - In primary disorders of renal tubular transport only the urine amino acids will be abnormal, thus these conditions will be missed if plasma alone is studied.

Based on the provided context, it appears that there are several diseases related to amino acid transport that have been considered for drug treatment.

• Urea cycle disorders: These disorders can be treated with dietary restriction of offending amino acids and sometimes medication (Context #3).
• Colitis: Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis, leading to an IL-17-predominant T cell response (Context #4).
• Metabolic disorders: Amino acid transporters are considered disease modifiers and drug targets in metabolic disorders such as diabetes and obesity (Context #10).
• Neurological disorders: Amino acid transporters are also considered drug targets in neurological disorders (Context #10).

In terms of specific drugs, the context mentions:

• Sodium benzoate, sodium phenylacetate, and arginine: These were shown to be effective in treating a condition (Context #8).
• Tetraethylammonium and tyramine: These are experimental drugs with no approved indication (Context #7).

It's worth noting that the context also mentions that there is currently no curative treatment available for certain diseases related to amino acid transport (Context #14).

The differential diagnosis of obsolete amino acid transport diseases involves identifying conditions that may present similarly to a specific disorder, in this case, an amino acid transport disease.

According to the search results, disorders of amino acid metabolism or transport are most clearly expressed in urine [11]. However, the interpretation of abnormalities in urinary amino acid excretion remains difficult, and an increase or decrease of almost every amino acid in urine can be due to various etiology [11].

To differentiate between primary and secondary aminoacido-pathies systematic laboratory investigation is necessary [10]. Early diagnosis of disorders of amino acid metabolism or transport is very important, because most of them can be treated, leading to the prevention of (further) clinical complications [10].

In addition, genetic defects in the synthesis, catabolism or transport of amino acids underlie a diverse class of diseases known as inborn errors of amino acid metabolism [14]. This includes disorders such as lysinuric protein intolerance (LPI), which is a rare inherited metabolic disorder that affects the transport of amino acids [7].

Other conditions that may be considered in the differential diagnosis of obsolete amino acid transport diseases include:

• Organic acidemias, which are a group of metabolic disorders caused by defects in the metabolism of organic acids [15].
• Ureagenesis defects, which are disorders that affect the production of urea from ammonia [1-3].
• Amino acid metabolism disorders, such as phenylketonuria (PKU) and maple syrup urine disease, which are inherited metabolic disorders caused by defects in amino acid metabolism [5].

It's worth noting that the diagnosis of these conditions often requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

References:

[1] NA Mew · 2017 [2] Jun 22, 2017 [3] Aug 23, 2016 [4] by MA Edwards · 1988 [5] by T IJzermans · 2023 [6] amino acid in urine can be due to various etiology. [7] Disorders of amino acid metabolism or transport are most clearly expressed in urine. [8] In those disorders, which cannot be treated, early diagnosis in an index-patient may prevent the birth of other siblings by means of genetic counseling and prenatal diagnosis. [9] Primary aminoacidopathies can be due to genetically determined transport disorders and enzyme deficiencies in amino acid metabolism or degradation. [10] This review intends to summarize and update all the conditions in which a strong association has been found between an amino acid transporter and an inherited metabolic disorder. [11] Genetic defects in the synthesis, catabolism or transport of amino acids underlie a diverse class of diseases known as inborn errors of amino acid metabolism.