3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.
2-Methyl-3-hydroxybutyryl CoA dehydrogenase deficiency (Hydroxyl-CoA dehydrogenase deficiency; MHBD) is a rare inborn disease of metabolism caused by a mutation in the HSD17B10 gene which codes for 3-hydroxyacyl-CoA dehydrogenase type-2. A deficiency in this enzyme results in accumulation of L-lactic acid in blood, spinal fluid, and urine; 2-ethylhydracrylic acid, 2-methyl-3-hydroxybutyric acid, and tiglylglycine in urine. Symptoms include cerebal atrophy, motor and mental retardation, overactivity and behavior issues, seizures and progressive neurological defects leading to early death. Treatment includes a high carbohydrate and low protein diet.
L-2-Hydroxyglutaric Aciduria (D-2-Hydroxyglutaric Aciduria ) is an autosomal recessive disease caused by a mutation in the L2HGDH gene which codes for L-2-Hydroxygluarate dehydrogenase. A deficiency in this enzyme results in accumulation of L-2-Hydroxyglutaric acid in plasma, spinal fluid, and urine; and L-lysine in plasma and spinal fluid. Symptoms, which present at birth, include ataxia, hypotonia, mental retardation, and seizures. Premature death often results. D-2-Hydroxyglutaric Aciduria is an autosomal recessive disease caused by a mutation in the D2HGDH gene which does for D-2-Hydroxygluarate dehydrogenase. A deficiency in this enzyme results in accumulation of D-2-Hydroxyglutaric acid in plasma, spinal fluid, and urine; oxoglutaric acid in urine; and gabba-aminobutyric acid in spinal fluid. Symptoms, which present at birth, include ataxia, hypotonia, mental retardation, and seizures. Premature death often results.
Argininosuccinic Aciduria, (Argininosuccinase Deficiency, Argininosuccinate Lyase Deficiency, ASL Deficiency) is an autosomal recessive disorder caused by a mutation in the ASL gene which codes for argininosuccinate lyase. It results in accumulation of citrulline, arginosuccinic acid, L-arginine, and L-glutamic acid in plasma as well as ammonia in blood. Infants are lethargic and unwilling to eat. They may develop seizures, coma, and failure to thrive as toxic ammonia accumulates.
CCarbamoyl Phosphate Synthetase Deficiency, also called hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a defective CPS1 gene. The CPS1 gene codes for the protein carbamoyl phosphate synthetase I, which plays a role in the urea cycle. This disorder is characterized by a large accumulation of ammonia in the blood. Symptoms of the disorder include unusual movements, seizures, unusual sleeping or coma. Treatment with citrulline or arginine, which maintains a regular rate of protein creation. It is estimated that carbamoyl phosphate synthetase deficiency affects 1 in 800,000 individuals in Japan.
Citrullinemia Type 1, also called argininosuccinate synthetase deficiency, argininosuccinic acid synthetase deficiency or ASS deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a deficiency of argininosuccinate synthetase. Argininosuccinate synthetase is an important enzyme in the process of removing nitrogen from the body. This disorder is characterized by a large accumulation of ammonia in the blood as well as other bodily fluids . Symptoms of the disorder include vomiting, lethargy and intracranial pressure. Treatment with protein restriction and intravenous administration of arginine can help manage symptoms, and diet management throughout the patient’s life can also show improvement. It is estimated that citrullinemia type 1 affects 1 in 57,000 individuals.
