HARTNUP DISEASE: Causes- Treatment- Symptoms- Signs- Diagnosis- USMLE-Mnemonic- Aminoaciduria
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HARTNUP DISEASE: Causes- Treatment- Symptoms-
HARTNUP DISEASE: Causes- Treatment- Symptoms- Signs- Diagnosis- USMLE-Mnemonic-Niacin Deficiency- Pellegra- Aminoaciduria
Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins.
Hartnup disease is caused by mutations in the SLC6A19 gene. This gene provides instructions for making a protein called B0AT1, which is primarily found embedded in the membrane of intestine and kidney cells. The function of this protein is to transport certain amino acids into cells.
What causes Aminoaciduria?
This may be caused by congenital disorders of amino acid metabolism, for example, phenylketonuria, or may be secondary to liver disease. In renal aminoaciduria, the renal tubules are unable to reabsorb the filtered amino acids back into the blood, causing high concentrations of amino acids in the urine
People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition
Other Names for This Condition
Hartnup disorder
Hartnup's disease
neutral amino acid transport defect
What are the symptoms of Hartnup disease?
skin rash.
anxiety.
rapid mood swings.
delusions.
hallucinations.
intention tremor.
speech difficulties.
unsteady wide-based gait, in which you walk with your legs farther apart than normal.
Synonyms of Hartnup Disease
Hartnup disorder
Hartnup syndrome
pellagra-cerebellar ataxia-renal aminoaciduria syndrom
Affected Populations
Hartnup disease affects both males and females in equal numbers. The disorder usually begins in childhood and continues into adulthood. The number of people affected by Hartnup disease is unknown. It has been estimated to occur at a frequency of approximately one in 30,000 individuals based upon newborn screening results in the United States and Australia.
Diagnosis
Due to the variability of symptoms, unambiguous diagnosis can only be made through urine analysis. Pediatricians can request this analysis from selected pathology centers. The test is based on the detection of elevated amino acids in the urine by chromatography and mass spectroscopy.
Molecular genetic testing can confirm a diagnosis of Hartnup disease in some cases. Molecular genetic testing can detect genetic alterations in the SLC19A6 gene known to cause the disorder, but usually is not necessary to obtain a diagnosis.
Hartnup disease manifests during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus, and tremor.
Nicotinamide is necessary for neutral amino acid transporter production in the proximal renal tubules found in the kidney, and intestinal mucosal cells found in the small intestine. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine. Pellagra, a similar condition, is also caused by low nicotinamide; this disorder results in dermatitis, diarrhea, and dementia.
A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic. All patients who are symptomatic are advised to use physical and chemical protection from sunlight: avoid excessive exposure to sunlight, wear protective clothing, and use chemical sunscreens with a SPF of 15 or greater. Patients also should avoid other aggravating factors, such as photosensitizing drugs, as much as possible
Diagnostic methods
Neutral hyperaminoaciduria (determined by urine chromatography) is the diagnostic hallmark. Diagnostic confirmation relies upon the mutation analysis of the SLCA19 gene (broad allelic heterogeneity).
Differential diagnosis
Pellagra is the main differential diagnosis. Blue diaper syndrome, ataxia-telangiectasia, hydroa vacciniforme, pityriasis alba, and xeroderma pigmentosum should be excluded.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Symptomatic subjects benefit from a high-protein diet, sunlight protection, and avoidance of photosensitizing drugs. Treatment includes nicotinamide supplements (40 to 200 mg per day). Some patients may respond to a tryptophan-rich diet. Patients with severe central nervous system involvement require neurologic and psychiatric treatment.
Prognosis
The presentation of the disorder is commonly benign. Hartnup disease probably does not adversely affect pregnancy and would be harmless to the fetus.
Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins.
Hartnup disease is caused by mutations in the SLC6A19 gene. This gene provides instructions for making a protein called B0AT1, which is primarily found embedded in the membrane of intestine and kidney cells. The function of this protein is to transport certain amino acids into cells.
What causes Aminoaciduria?
This may be caused by congenital disorders of amino acid metabolism, for example, phenylketonuria, or may be secondary to liver disease. In renal aminoaciduria, the renal tubules are unable to reabsorb the filtered amino acids back into the blood, causing high concentrations of amino acids in the urine
People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition
Other Names for This Condition
Hartnup disorder
Hartnup's disease
neutral amino acid transport defect
What are the symptoms of Hartnup disease?
skin rash.
anxiety.
rapid mood swings.
delusions.
hallucinations.
intention tremor.
speech difficulties.
unsteady wide-based gait, in which you walk with your legs farther apart than normal.
Synonyms of Hartnup Disease
Hartnup disorder
Hartnup syndrome
pellagra-cerebellar ataxia-renal aminoaciduria syndrom
Affected Populations
Hartnup disease affects both males and females in equal numbers. The disorder usually begins in childhood and continues into adulthood. The number of people affected by Hartnup disease is unknown. It has been estimated to occur at a frequency of approximately one in 30,000 individuals based upon newborn screening results in the United States and Australia.
Diagnosis
Due to the variability of symptoms, unambiguous diagnosis can only be made through urine analysis. Pediatricians can request this analysis from selected pathology centers. The test is based on the detection of elevated amino acids in the urine by chromatography and mass spectroscopy.
Molecular genetic testing can confirm a diagnosis of Hartnup disease in some cases. Molecular genetic testing can detect genetic alterations in the SLC19A6 gene known to cause the disorder, but usually is not necessary to obtain a diagnosis.
Hartnup disease manifests during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus, and tremor.
Nicotinamide is necessary for neutral amino acid transporter production in the proximal renal tubules found in the kidney, and intestinal mucosal cells found in the small intestine. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine. Pellagra, a similar condition, is also caused by low nicotinamide; this disorder results in dermatitis, diarrhea, and dementia.
A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic. All patients who are symptomatic are advised to use physical and chemical protection from sunlight: avoid excessive exposure to sunlight, wear protective clothing, and use chemical sunscreens with a SPF of 15 or greater. Patients also should avoid other aggravating factors, such as photosensitizing drugs, as much as possible
Diagnostic methods
Neutral hyperaminoaciduria (determined by urine chromatography) is the diagnostic hallmark. Diagnostic confirmation relies upon the mutation analysis of the SLCA19 gene (broad allelic heterogeneity).
Differential diagnosis
Pellagra is the main differential diagnosis. Blue diaper syndrome, ataxia-telangiectasia, hydroa vacciniforme, pityriasis alba, and xeroderma pigmentosum should be excluded.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Symptomatic subjects benefit from a high-protein diet, sunlight protection, and avoidance of photosensitizing drugs. Treatment includes nicotinamide supplements (40 to 200 mg per day). Some patients may respond to a tryptophan-rich diet. Patients with severe central nervous system involvement require neurologic and psychiatric treatment.
Prognosis
The presentation of the disorder is commonly benign. Hartnup disease probably does not adversely affect pregnancy and would be harmless to the fetus.
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