disruption of β-cystathionine synthetase activity (catalyzes the formation of cystathion from homocysteine and serine)
clinical picture: the manifestations are not obvious immediately after birth, but in further development there are symptoms affecting various tissues and organs
they appear in toddler or preschool age - a disorder of mental development (psychomotor retardation in 60% of cases[2]), marfanoidphenotype (tall slender stature, arachnodactyly, kyphosis, scoliosis, osteoporosis),glaucoma and central and peripheral thromboembolic events,
dislocations of lenses cause strong myopia, thromboses occur most often at the base of the skull and are life-threatening. Thanks to thrombosis, gangrene of the organs occurs, which usually ends the patient's life in the 20s-30s. a year
laboratory: increased homocysteine and methionine in the blood, frequent metabolic osteopathy
must be confirmed at the enzymatic and molecular level
dif.dg: homocysteinemia is also present with - disorders of the metabolism of methylmalonic acid, cobalamin or with B6 deficiency
therapy: some patients (approx. 50%[2]) respond favorably to high doses of pyridoxine (vit B6) (in the amount of 300-900 mg/ d[2]), which is a cofactor of β-cystathionine synthetase
in case of complete lack of enzymatic activity, it is necessary to start dietary treatment with limited supply of methionine and supply of cystine
this is a defect in the lysosomal transport of cystine, which leads to its storage
accumulation affects the RES (spleen, liver, nodes and bone marrow), deposits can also be demonstrated in the cells of the kidney tubules (primarily proximal) and conjunctiva
clinical manifestations are visible only in the kidneys, where there is a severe violation of their function
'laboratory: manifestations of kidney damage and their prox. tubule – glycosuria, phosphaturia, albuminuria, hyperaminoaciduria, chronic acidosis and uremia together is called proximal tubular syndrome or also Fanconi syndrome. '
all aminoaciduria is due to gradual impairment of GF (glomerular filtration), which soon results in kidney failure
clinical picture: in the second half of the first year there is polydipsia, polyuria, dehydration, metabolic acidosis, photophobia and hypophosphatemic rickets'
therapy: symptomatic treatment of tubular dysfunction (supply of electrolytes and fluids), usually high doses of vitamin D are necessary (increase in intestinal phosphate absorption and decrease in urinary phosphate excretion)[2]
by administration of cysteamine, which works in two ways
by binding to cystine, it creates cysteine, which can be excreted from the lysosome using the cysteine transporter[2]
by binding to cystine, cysteine-cysteamine disulfide is formed, which can be excreted from the lysosome by means of the lysine transporter[2]
diagnosis: can be determined by examining the eyes, as cystine crystals are also deposited in the cornea and is further proven biochemically by determining the concentration of cystine in leukocytes or cultured fibroblasts, which is increased 50-100 times.
congenital disorder of the transport of dibasic AMKs -''cystine, lysine, ornithine and arginine in kidney tubules and in the intestine
clinical picture: cystine nephrolithiasis, which is caused by the poor solubility of cystine in water and further by its crystallization in an acidic environment
'diagnosis: increased levels of cystine, ornithine, arginine, lysine in urine; kidney and excretory system[2]
therapy: the aim is to prevent nephrolithiasis and therefore a high fluid intake (4-5l) combined with night drinking is recommended
only in severe cases it is possible to consider drug therapy with D-penicillamine (as the treatment has many side effects) or mercaptopropionylglycine, which causes the formation of more soluble bisulfides with cystine[2]
