HOMOCYSTINURIA

( AN INBORN
METABOLIC DISORDER)
 Ectopia lentis
 Luxation of lens
 Myopia
 Glaucoma
 Optic atrophy
 Retinal
detachment
 Loss of vision
 Limbs grow out of
proportion.
 Anterior chest deformities. feature of
 homocystinuria
Most distinguishing
is specially
osteoporosis spinal osteoporosis.
 Long spindly arms and legs.
 Thromboembolism
 Abnormal blood clots
 Intravascular
thrombosis
 strokes
 Mental retardation
 Low IQ
 Episodic depression
 Behavioral
disorders
 Schizophrenia
 If both parents carry the faulty gene, for
each child, there is a:
 25% chance the child will be born with the
disorder
 50% chance the child will be a carrier of the
faulty gene
 25% chance the child will neither
have disorder nor would be the carrier.
 It is present at the time of birth but its
symptoms are often remain un noticed in
new born babies.
 New born babies are tested
homocystinuri befor for they
a hospital. e leave
the
 Normal Homocysteine
Levels

 in the blood between 4 and

15 micromoles/liter (µmol/L).
 Any measurement above 15 is
considered high.
 Any measurement below 12 is
considered low.
 Optimal homocysteine levels are
below 10 to 12.
 if a child is not tested at the time of birth, a
doctor may later discover the disorder based
on symptoms. At that point the following
be done:
 Blood tests to confirm the diagnosis
 x-rays to look for bone problems
 An eye exam to look for eye problems
 No specific cure has been discovered for
homocystinuria; however many are
treated using high doses of vitamin
people
Pyridoxine.
B6 ie
 Slightly less than 50% respond to this treatment.
and need to intake supplemental vitamin B6
and for the rest of their lives.
 Those who do not respond require a low
methionine diet .
 Most will need treatment with trimethylglycine.
 It is used to reduce the concentration of
homocysteine by promoting the conversion
of homocysteine back to methionine.

The re-formed methionine is then
gradually removed by incorporation into
body protein.

The methionine that is not converted into
protein is converted to S-
adenosylmethionine which goes on to form
homocysteine again.
 Betaine is therefore only effective if the
quantity of methionine to be removed is
small. Hence treatment includes both
betaine and a diet low in methionine.

 In classical homocystinuria (CBS deficiency)

the plasma methionine usually increases
above the normal and the
shoul concentration be monitoredas
levels
d may bepotentially toxic
reached.
 Genetic counseling is recommended for prospective
parents with a family history of homocystinuria
 Prenatal diagnosis of homocystinuria is available and
is made by culturing amniotic cells or chronic villi to
test for the presence or absence of
Cystathionine synthase ( the enzyme
that is missing in
homocystinuria).
 If the diagnosis is made while a patient is young, a
low methionine diet started promptly and strictly
adhered to can spare some mental retardation and
other complications of this disease.
 Blood clot
 Damaged vision
 Intellectual disability.
 Coronary artery disease - e.g.,
myocardial infarction
 osteoporosis
 Fatty infiltration of liver
 Blood clotting which could lead to
heart strokes.
 Kraus JP, Janosík M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G,
de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB,
Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M. Cystathionine
beta- synthase mutations in homocystinuria. Hum Mutat. 1999;13(5):362-75.
Review. PubMed citation.
 Banerjee R, Zou CG. Redox regulation and reaction mechanism of human
cystathionine-beta-synthase: a PLP-dependent hemesensor protein. Arch
Biochem Biophys. 2012 Jan 1;433(1):144-56.
 Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of
Dermatology, Venereology and Allergology, Wroclaw Medical University;
Director of the Institute of Immunology and Experimental Therapy, Polish
Academy of Sciences, Poland.
 Champe, PC and Harvey, RA. "Biochemistry. Lippincott's Illustrated Reviews" 4th
ed. Lippincott Williams and Wilkins, 2008.
 Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier
Saunders. p. 1362.
 de Ruijter, W. et al, “Use of Framingham risk score and new biomarkers to
predict cardiovascular mortality in older people: population based observational
cohort study”. British Medical Journal, 2013.