INBORN ERRORS OF

AMINOACID
METABOLISM
🄿🅁🄴🅂🄴🄽🅃🄴🄳 🄱🅈
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◦ ꜰɪᴅʜᴀ ꜱʜyʀɪɴ
◦ ᴍɪᴅʜᴜʟᴀᴊ ᴍ ꜱ
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◦ ꜱɪᴅʜᴀʀᴛʜ ᴏ
🇮🇳🇹🇷🇴🇩🇺🇨🇹🇮🇴🇳
                       
A number of inborn errors of aminoacids metabolism are known.
They occur due to genetically determined deficency or absence or modification of a specific protein.
ᴅɪꜱᴏʀᴅᴇʀꜱ ᴏꜰ Aa ᴍᴇᴛᴀʙᴏʟɪꜱᴍ ɪꜱ
ᴄʟᴀꜱꜱɪꜰɪᴇᴅ ɪɴᴛᴏ:
# disorders of aromatic Aa metabolism
# disorders of branched Aa metabolism
# inborn errors of histidine metabolism
# inborm errors of sulphur containing Aa metabolism
# other inborn errors
ᴅɪꜱᴏʀᴅᴇʀ ᴏꜰ ᴀʀᴏᴍᴀᴛɪᴄ Aa
ᴍᴇᴛᴀʙᴏʟᴏꜱᴍ
$This include:
¥ phenylketonuria
¥ alkaptonuria
¥ tyrosinaemia
¥ albinism
ᴩʜᴇɴyʟᴋᴇᴛᴏɴᴜʀɪᴀ (PKU)
Definition
PKU is a rare hereditary condition in which the amino acid phenylalanine Is not properly metabolized.

Cause
Phenylketonuria (PKU) is inherited as an autosomal recessive trait (both parents must pass on the defective gene
for the child to be affected). The genetically determined abnormality in phenylketonuria is a missing enzyme
called phenylalanine hydroxylase.

Risks
Damage to the brain causes marked mental retardation by the end of the first year of life if the offending proteins
are not avoided. Older children may develop movement disorders (athetosis), rocking and hyper activity.
ᴩʀᴇᴠᴇɴᴛɪᴏɴ
Genetic counseling is recommended for prospective parents with a family history of PKU. The carrier state
for PKU can be detected by enzyme assays, and PKU can be diagnosed prenatally.

It is imperative that women with PKU who becomes pregnant adhere closely to the special low-
phenylalanine diet, since accumulation of phenylalanine will damage the unborn baby even if the baby has
not inherited the abnormality.
Symptoms
Skin rashes (ecsema)
Microcephaly
Tremors.
Jerking movements of the arms or legs spasticity.
Unusual hand posturing
Seizures.
Hyperactivity Delayed mental and social skills
Mental retardation.
A distinctive “mousy” odor to the urine and sweat
Light coloration (frequent finding of light complexion, blond hair, and blue eyes)
Tests
Tests include:
Enzyme assay to detect the carrier state (parents)
Chorionic villus sample to detect fetal PKU (prenatal diagnosis)
PKU screening (a heelstick blood sample from the infant to screen for PKU, mandatory in most states)

Complications
.Severe mental retardation occurs if the disorder is untreated.
ALKAPTONURIA
Definition
Alkaptonuria is a rare inherited disorder of metabolism characterized by urine which turns black when
exposed to air. Another characteristic is the development of arthritis in adulthood
.Alternative Names
Alcaptonuria; Homogentisic acid oxidase deficiency; Ochronosis
Black urine disease, Black bone disease.
Sign
> In children:
• urine in diaper may darken
➤ In adults:
◦ darkening of the ear
• dark spots on the on thesclera and cornea•
arthritis
TYROSINAEMIA
There are 3 types of tyrosinaemia:
Tyrosinaemia type1
◦ Due to deficency of fumaryl acetoacetate hydrolase
◦ Accumulation of fumaryl acetoacetate cause a cabbage like order, abnormal liver function and renal
tubular dysfunction
Tyrosinaemia type 2
◦ Manifests painful corneal erosion and plaques, inflammation and mental retardation
Transient Tyrosinaemia
◦ Most common form in infancy
◦ Due to absence of enzyme p-hydroxyphenylpyruvate dioxygenase
ALBINISM
Albinism: refers to a group of related conditions. These conditions are the result of altered genes that cause
a defect of melanin production. This defect results in the partial or full absence of pigment from the skin,
hair, and eyes.
Cause
• An amino acid called tyrosine is normally converted by the body to the pigment melanin. Albinism
results when the body is unable to produce or distribute melanin because of one of several possible defects.
In particular, defects in the metabolism of tyrosine leading to failure to convert it into melanin, can cause
albinism.
Risk
Affected people may appear to have hair, skin, and iris color that are white as well as vision defects. They
also have photophobia (sunlight is painful to their eyes), they sunburn easily, and do not tan.
Albinism have some of the following possible symptoms:

Rapid eye movements (nystragmus)

. Strabismus (eyes not tracking properly)

. Photophobia (avoidance of light because of discomfort)

Decreased visual acuity.

Functional blindness.
DISORDERS OF BRANCHED
CHAIN AMINOACIDS
◦ MAPLE SYRUP DISEASE
◦ ISOVALERIC ACIDAEMIA
◦ METHYL MALONIC ACIDURIA
MAPLE SYRUP URINE DISEASE
(MSUD)
Definition
Maple syrup urine disease is an inherited disease of amino acid metabolism that causes acidosis, central
nervous system symptoms, and urine that may smell sweet like maple syrup.

Causes
Maple syrup urine disease (MSUD) is caused by the inability to metabolize the branched-chain amino
acids leucine, isoleucine, and valine. The disease is called MSUD because urine from affected people
smells like maple syrup.
Risk factors
• In the most severe form, MSUD causes severe acidosis during the first week of life. This is characterized
by progressively poorer feeding, vomiting, seizures, lethargy, and finally coma.
◦ • Untreated infants may die in the first few weeks of life in severe forms of the disease. MSUD also
occurs in an intermittent form and a mild form. Even in the mildest form, infaections can cause mental
retardation and bouts of acidosis
◦ .Signs
◦ • Urine amino acids (elevated levels of the amino acids leucine, isoleucine, and valine)
◦ Plasma amino acids (elevated levels of leucine, isoleucine, and valine)
◦ Ketosis (elevated levels of ketone
◦ bodies in urine and plasma)
◦ Acidosis (excess acid in blood)
ISOVALERIC ACIDAEMIA
◦ Due to deficiency of isovaleryl CoA dehydrogenase.
◦ Accumulation of plasma isovalerate cause frequent episodes of vomiting, acidosis, and coma of children,
which emit a characteristic body odour
METHYL MALONIC ACIDURIA
◦ Due to defective methylmalonyl CoA mutase, which converts methylmalonylCoA to succinyl CoA
INBORN ERRORS OF HISTIDINE
METABOLISM
◦ HISTIDINAEMIA
HISTIDINAEMIA
◦ Due to deficency of histidase which converts histidine to urocanate.
◦ Accumulation of histidine result in the formation of an alternate metabolite imidazole pyruvate and their
urinary excretion
INBORM ERRORS OF SULPHUR
CONTAINING AMINO ACIDS
◦ HOMOCYSTINURIA
◦ CYSTINURIA
◦ CYSTINOSIS
HOMOCYSTINURIA
Definition:
Homocystinuria is an inherited disorder of the metabolism of the amino acid methionine.

Alternative Names:
Cystathionine beta synthasedeficiency

Causes
Homocystinuria is inherited as an autosomal recessive trait, which means that the child must inherit the
defective gene from both parents to be seriously affected.
Risk
◦ Usual findings in homocystinuria are nearsightedness, dislocation of the lens of the eye, and a tendency to develop
blood clots in the veins and arteries. Mental retardation and failure to thrive.

◦ Symptoms

A family history of homocystinuria Nearsightedness

Flush across the cheeks
Tall, thin build
Long limbs
High-arched feet (pes cavus)
◦ Knock-knees (genu valaum) •
◦ Pectus excavutum .
◦ • Pectus carinatum
◦ • Mental retardation
◦ . Psychiatric disease
CYSTINURIA
◦ It is a diorder of renal and gi tract transport of cystine
◦ Cystine may precipitate in the renal tubules to form cystine calculi
CYSTINOSIS
Definition :
◦ Cystinosis is a metabolic disease characterized by an abnormal accumulation of the amino acid cystine in
various organs of the body such as the kidney, eye, muscle, pancreas, and brain. Different organs are
affected at different ages.
◦ CAUSES
◦ The cystine content of cystinotic cells averages 50-100 times the normal value. The cause is a defect in
the transport of cystine out of a cell compartment called the lysososme, in which cystine accumulates.
Because of cystine’s low solubility, this amino acid forms crystals within the lysosomes of cells, and this
is probably what destroys the cells.
Forms of cystinosis

There are three clinical forms of cystinosis. Infantile (or nephropathic) cystinosis; late-onset cystinosis; and
benign cystinosis.

SYMPTOMS

◦ thirst and urination, failure to thrive, rickets, and episodes of dehydration. And kidney damage. But
benign cystinosis not produce kidney damage
OTHER INBORN ERRORS
Hartnup disease
Non ketotic hyperglycinaemia
HARTNUP DISEASE
◦ Impairment of transport of neutral aminoacids in the intestinal mucosa and renal tubules causes this rare
autosomal recessive disease.
◦ Neurological symptoms of hartnup disease are due to bacterial degradation of tryptophan in gi tract
forming indolyl acetic acid and indolyl acetyl amine
NON KETOTIC
HYPERGLYCINAEMIA
◦ This is a rare autosomal reccessive disease is due to absence of enzyme glycine synthase resulting in the
increased levels of plasma gycine and its excretion in urine.