Inborn Errors of Amino Acid Metabolism Medical Assignment Help

Inborn errors of amino acid metabolism are chiefly inherited as autosomal recessive conditions.

Amino acid transport defects

Amino acids are filtered by the glomerulus but 95% of the filtered load is reabsorbed in the proximal convoluted tubule by an active transport mechanism. Aminoaciduria results from:
• Abnormally high plasma amino acid levels (e.g. phenylketonuria)
• Any inherited disorder that damages the tubules secondarily (e.g. galactosaemia)
• Tubular reabsorptive defects, either generalized (e.g. Fanconi syndrome) or specific (e.g. cystinuria)
• Amino acid transport defects can be congenital or acquired.


Fanconi syndrome

This occurs in a juvenile form (De Toni-Fanconi-Debre syndrome); in adult life it is often acquired due to, for .example, heavy metal poisoning, drugs or some renal diseases. There is defective tubular reabsorption of:
• Most amino acids
• Glucose
• Urate
• Phosphate, resulting in hypophosphataemic rickets
• Bicarbonate, with failure to transport hydrogen ions, causing a renal tubular acidosis that then produces a hyperchloraemic acidosis

Other abnormalities include:
• Potassium depletion, primary or secondary to the acidosis
• Polyuria
• Increased excretion of immunoglobulins and other low-molecular-weight proteins
Various combinations of the above abnormalities have been described.
The juvenile form begins at the age of 6-9 months, with failure to thrive, vomiting and thirst. There is also acidosis, dehydration and vitamin D-resistant rickets. In the adult, the disease is similar to the juvenile form, but osteomalacia is a major feature.
Treatment is with large doses of vitamin D (e.g. 1-2 J.Lg of l o-hydroxycholecalciferol with regular blood calcium monitoring).

Lowe’s syndrome (oculocerebrorenal dystrophy)

In this syndrome there is generalized aminoaciduria combinedwith mental retardation, hypotonia, congenital cataracts  and an abnormal skull shape.



There is defective tubular reabsorption and jejunal absorption of cystine and the dibasic amino acids lysine, ornithine and arginine. Inheritance is either completely or incompletely recessive, so that heterozygotes who have increased excretion of lysine and cystine only can occur. Cystine absorption from the jejunum is impaired but, nevertheless, cystine in peptide form can be absorbed. Cystinuria leads to urinary stones and is responsible for approximately 1-2% of all urinary calculi. The disease often starts in childhood, although most cases present in adult life.

Treatment is with a high fluid intake in order to keep the urinary cystine concentration low. Patients are encouraged to drink up to 3 litres over 24 hours and to drink even at night. Penicillamine should be used for patients who cannot keep the cystine concentration of their urine low.
The condition cystinosis must not be confused with cystinuria.

Hartnup’s disease

There is defective tubular reabsorption and jejunal absorption of most neutral amino acids but not their peptides. The resulting tryptophan malabsorption produces nicotinamide deficiency. Patients can be asymptomatic, but others develop evidence of pellagra, with cerebellar ataxia, psychiatric disorders and skin lesions. Treatment is with nicotinamide and often brings about considerable improvement.

Tryptophan malabsorption syndrome (blue diaper syndrome)

This is due to an isolated transport defect for tryptophan; the tryptophan excreted oxidizes to a blue colour on the baby’s diaper.

Familial iminoglycinuria

This occurs when there is defective tubular reabsorption of glycine, proline and hydroxyproline. It seems to have few clinical effects.

Methionine malabsorption


This is due to failure to absorb and excrete methionine, and results in diarrhoea, vomiting and mental retardation. Patients characteristically have an oast-house smell.

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