Browsing Pathways

Glutaric Aciduria Type 1 is a rare autosomal recessive disease caused by a mutation in the GCDH which codes for glutaryl-CoA dehydrogenase. A deficiency in this enzyme results in accumulation of 3-hydroxybutyric acid, 3-hydroxyglutaric acid, glutaconic acid, glutaric acid, and ketone bodies in urine. Symptoms include encephalopathy, grimacing, dystonia, metabolic acidosis, and hygroma. Treatment includes a low-protein diet, L-carnitine, riboflavin, and anticonvulsants.

SGLT2 is a sodium/glucose co-transporter that exists almost exclusively in kidney tissue. It is responsible for approximately 90% of the kidney's reabsorption of glucose, and can be found in the S1 segment of the proximal convoluted tubule of the nephron. A defect in the SLC5A2 gene that codes for SGLT2 results in glucosuria, due to the inability of most of the glucose to be reabsorbed by the kidney. There are some drugs that inhibit SGLT2 and are used to decrease blood sugar in patients with type 2 diabetes mellitus.

Gamma-Glutamyltransferase Deficiency is an autosomal recessive disorder caused by a mutation in the GGT1 gene which codes for gamma-glutamyltranspeptidase 1. A deficiency in this enzyme results in accumulation of L-cysteine, gamma-glutamylcysteine, and glutathione in urine. Symptoms, which present at birth, include tall stature, psychosis, and mental retardation.

Galactosemia (GALT Deficiency; GALT; Galactose-1-Phosphate Uridylyltransferase Deficiency) is a rare genetic disorder caused by a mutation in the GALT gene which codes for galactose-1-phosphate uridylyltransferase. A deficiency in this enzyme results in accumulation of D-galactose and galactitol in plasma and urine; bilirubin, chloride, and galactose-1-phosphate, and transaminases in serum. Symptoms, which present at birth, include jaundice, enlarged liver, anemia, weight loss, and vomiting. Treatment includes galactose-free diet, antibiotics, and vitamin K.

Ethylmalonic Encephalopathy (Epema Syndrome; EE) is a rare autosomal recessive disorder caused by a mutation in the ETHE1 gene which codes for protein ETHE1. A deficiency of this protein inhibits proper energy production in mitochondria and a deficiency in cytochrome c oxidase. This results in accumulation of 2-methylbutyrylglycine, N-butyrylglycine, isobutyrylglycine, isovalerylglycine, and methylsuccinic acid in urine. Concentrations of L-carnitine are reduced in plasma. Symptoms, which present at birth, include peripheral neuropathy, seizures, microcephaly, and hypotonia lead to premature death. Treatment includes riboflavin and L-carnitine.

Dihydropyrimidine Dehydrogenase Deficiency (DHPD; Thymine-uraciluria) is a rare autosomal recessive disorder caused by a mutation in the DPYD gene which codes for dihydropyrimidine dehydrogenase. A deficiency in this enzyme results in accumulation of 5-hydroxymethyluracil, thymine, and uracil in urine. Symptoms include nystagmus, large liver, hypotonia, growth and mental retardation, and seizures.

Dihydropyrimidinase Deficiency (DHPA, Dihydropyrimidinuria Deficiency, DPH Deficiency) is an autosomal recessive disease caused by a mutation in the DPYS gene which codes for dihydropyrimidinase. A deficiency in this enzyme results in accumulation of dihydrothymine, dihydrouracil, thymine, and uracil in urine. Symptoms, which present at birth, include metabolic acidosis, difficulty feeding, and seizures.

Cystathionine Beta-Synthase Deficiency (CBS Deficiency; Homocystinuria) is an autosomal recessive disease caused by a mutation in the CBS gene which codes for cystathionine beta-synthase. A deficiency in this enzyme results in accumulation of L-cystathionine, homocysteine, and L-homocystine in plasma and urine; and L-methionine and ornithine in plasma. Symptoms include osteoporosis, myopia, fatty-liver, mental retardation, and early death. Treatment includes folic acid, vitamin B6, vitamin B12, and a methionine-restricted diet.

Canavan Disease (Canavan-Van Bogaert-Bertrand Disease; Aminoacylase 2 Deficiency; Spongy Degeneration of the Central Nervous System; Aspartoacylase Deficiency; ASP Deficiency; ACY2 Deficiency; ASPA) is a rare autosomal recessive disease caused by a defect in the ASPA gene which codes for aspartoacylase. A deficiency in this enzyme results in accumulation of N-Acetyl-L-aspartic acid in plasma, spinal fluid, and urine. Symptoms, which present at birth, include myclonus, irritability, hypotonia, motor retardation, and poor head control. The neurological complications are due to demyelination of neurons and leukodystrophy. Premature death often results, though lithium citrate can be used as a treatment.

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.