Synthase deficiency

Itzhak, Y., Gandia, C., Huang, P.L., Ali, S.F. Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity. J. Pharmacol. Exp. Ther. 284 1040, 1998. 

Methionine synthase deficiency (cobalamin-E disease) produces homocystinuria without methylmalonic aciduria 677 Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12 677 Hereditary folate malabsorption presents with megaloblastic anemia, seizures and neurological deterioration 678... 

Other causes of PKU secondary to defective tetrahydrobiopterin synthesis include GTP cyclohydrolase deficiency and 6-pyravoyltetrahydrobiopterin synthase deficiency. Patients with either defect have psychomotor retardation, truncal hypotonia with limb hypertonia, seizures and a tendency to hyperthermia. The intravenous administration of BH4 may lower blood phenylalanine levels but this cofactor may not readily cross the blood-brain barrier. Treatment with synthetic pterin analogs or supplementation with tryptophan and carbidopa may prove more efficacious, particularly if treatment is started early in life. 

Biochemical findings are variable. The blood cobala-min and folate levels often are normal. Patients often have homocysteinemia with hypomethioninemia, the latter finding discriminating this group from homocystinuria secondary to cystathionine- P-synthase deficiency. Urinary excretion of methylmalonic acid may be high, reflecting the fact that vitamin B12 serves as a cofactor for the methyl-malonyl-CoA (coenzyme A) mutase reaction. 

PHOTO-BIOLOGICAL HYDROGEN PRODUCTION BY THE UPTAKEHYDROGENASE AND PHB SYNTHASE DEFICIENT MUTANT OF RHODOBACTER SPHAEROIDES... 

Acute Intermittent Porphyria Uroporphyrinogen-I Synthase Deficiency... 

Answer C Only methionine is degraded via the homocysteine/cystathionine pathway and would be elevated in the plasma of a cystathionine synthase-deficient patient via activation of homocysteine methyl-transferase by excess substrate. 

Figure 9-5. Pathway for formation of cysteine from methionine. Only the enzymes involved in known diseases of this pathway are shown. Cystathionase is deficient in cysthioninuria, which leads to accumulation of cystathionine without producing frank symptoms. Cystathionine p-synthase deficiency causes homocystinuria.

The major type is caused by cystathionine fi-synthase deficiency, leading to accumulation of upstream intermediates in the pathway, especially homocysteine. 

The answer is A. The constellation of symptoms exhibited by this patient is characteristic of homocystinuria. The impairment of her cognitive function could be attributed to many conditions, but the key findings are ectopia lentis with downward lens dislocation and osteoporosis in a female of this age. Homocystinuria is produced by inherited deficiency of one of the enzymes in the pathway of Met conversion to Cys. The most common form is cystathionine P-synthase deficiency, which results in accumulation of all upstream components of the pathway, including homocysteine, which is responsible for the toxic effects, and Met, which becomes elevated in the blood. Cystathionine and cysteine, which are both downstream of the block in the pathway caused by cystathionine P Synthase deficiency, would be decreased. Metabolic pathways for lactate and urea are not involved in this disease mechanism. 

Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M. Restoration of ure-agenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr 2004 145(4) 552-4. 

Gammie SC, Nelson RJ (1999) Maternal aggression is reduced in neuronal nitric oxide synthase-deficient mice. J Neurosci 19 8027-8035 Caspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin news from mouse molecular genetics. Nat Rev Neurosci 4 1002-1012 Gobbi G, Murphy DL, Lesch K, Blier P (2001) Modifications of the serotonergic system in mice lacking serotonin transporters an in vivo electrophysiological study. J Pharmacol Exp Ther 296 987-995... 

Davis M, Myers KM (2002) The role of glutamate and gamma-aminobutyric acid in fear extinction clinical implications for exposure therapy. Biol Psychiatry 52 998-1007 Dawson VL, Kizushi VM, Huang PL, Snyder SH, Dawson TM (1996) Resistance to nemotox-icity in cortical cultures from neuronal nitric oxide synthase-deficient mice. J Nemosci... 

Gammie, S.C., and Nelson R.J. (1999) Maternal aggression is reduced in neuronal nitric oxide synthase-deficient mice./ Neurosci 19 8027-8035. 

Taylor, L.P. and Jorgensen, R., Conditional male fertility in chalcone synthase-deficient petunia. 

Alkyl-dihydroxyacetone phosphate (DHAP) synthase Isolated alkyl-DHAP synthase deficiency... 

N-Acetylglutamate synthase deficiency p Glut, Cit, Argt, Lysj... 

Carbamyl phosphate synthase deficiency p Glnt, Citt, Alat, Lyst... 

Pyrroline-5-carboxylate synthase deficiency p Prof, Ornj, Citp, ArgP... 

ASA-lyase deficiency Pyruvate carboxylase deficiency LPI Pyrroline-5-carboxylate synthase deficiency... 

Proline Prolinemia type 1 and 2 Lactic acidemias P-5-C synthase deficiency... 

Methionine synthase deficiency (cblC, cblD, cblF, cblE, cblG defects) 100-250... 

D-bifunctional protein deficiency [5], 2-methyl acyl-CoA racemase (AMACR) deficiency [3] and sterol carrier protein (SCP-x) deficiency [6], the disorders of etherphospholipid biosynthesis (dihydroxyacetone phosphate acyltransferase and alkyl- dihydroxyacetone phosphate synthase deficiency) [2], the disorders of phytanic acid alpha-oxidation (Refsum disease) [15], and the disorders of glyoxylate detoxification with hyperoxaluria type 1 as caused by alanine glyoxylate aminotransferase deficiency as a sole representative. 

Glycogen synthase is the enzyme deficient in glycogen synthase deficiency, also called glycogenosis type 0 (GSD 0, MIM 240 600). 

Gitzelmann R, Spycher MA, Feil G, Muller J, Seilnacht B, Stahl M, Bosshard, NU (1996) Liver glycogen synthase deficiency a rarely diagnosed entity. Eur J Pediatr 155 561-567... 

Table 5.3.11 Steroid excretion and diagnostic ratios in infants with pseudohypoaldosteronism (PHA) and aldosterone synthase deficiency (ASD)...

White PC (2004) Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol 217 81-87... 

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