Browsing Pathways

Leigh Syndrome, also called Leigh Disease or infantile subacute necrotizing encephalopathy, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder that is caused by a mutation of any one of 75 different genes. Disruptions of the complexes I or IV are the most common reasons for Leigh syndrome. Complex IV is crucial in the electron transfer steps of oxidative phosphorylation, which is needed to provide energy to the mitochondria. This disorder is characterized by a large accumulation of lactate in the body. Symptoms of the disorder include diarrhea, dysphagia and vomiting. There is no cure for Leigh syndrome and the loss motor skills degenerate rapidly. It is estimated that Leigh syndrome affects 1 in 40,000 individuals.

Iminoglycinuria, also called familial iminoglycinuria, is an autosomal recessive disorder of renal reabsorption caused primarily by a defective SLC36A2 gene. SLC36A2 codes for a proton-coupled amino acid transporter which facilitates the reuptake of glycine, proline, and hydroxyproline. This disorder is characterized by a large accumulation of glycine, proline, and hydroxyproline in the urine. Symptoms of the disorder include urolithiasis and mental retardation.

Hypoacetylaspartia, also known as N-acetylaspartate (NAA) deficiency is an extremely rare autosomal recessive inborn error of metabolism (IEM) caused by a mutation in the NAT8L gene. This gene encodes the N-acetylaspartate synthase protein, which catalyzes the formation of N-acetyl-L-aspartate from L-aspartate and acetyl-CoA, with CoA and a hydrogen ion being byproducts. This reaction occurs as part of the aspartate metabolism pathway. This disorder is characterized by a deficiency of NAA in the brain, as shown by magnetic resonance spectroscopy (MRS). Symptoms of the disorder include microcephaly, developmental delays, ataxia and seizures, which have been shown to worsen the ataxia. So, only one patient has been diagnosed with Hypoacetylaspartia.

Histidinemia (Histidine Ammonia-Lyase Deficiency; HAL Deficiency; Histidase Deficiency; HIS Deficiency) is an autosomal recessive disease caused by a mutation in the HAL gene which codes for hisitidine ammonia-lyase. A deficiency in this enzyme results in accumulation of L-histidine in serum, spinal fluid, and urine; histamine in plasma and urine; and imidazoleacetic acid, imidazolactic acid, and 1-methylhistamine in urine. Symptoms include organic acids in urine, mental retardation, and delayed speech development. Treatment includes a low-histamine diet.

Hawkinsinuria (4-Hydroxyphenylpyruvate Hydroxylase Deficiency) is an autosomal dominant disease caused by a mutation in the HPD gene which codes for 4-hydroxyphenylpyruvate dioxygenase. A deficiency in this enzyme results in accumulation of hawkinsin in urine and plasma; cis-4-hydroxycyclohexylacetic acid, trans-4-hydroxycyclohexylaceid, vanillactic acid, 4-hydroxyphenylpyruvic acid, pyroglutamic acid in urine; and L-tyrosine in plasma. Symptoms include ketosis, metabolic acidosis, swimming-pool odor, and mental retardation. Treatment includes a low-protein diet and vitamin C.

Hartunup Disorder (HND, Hartnup Disease) is an autosomal recessive disease caused by a mutation in the SLC6A19 which codes for sodium-dependent neutral amino acid transporter B(0). A deficiency in this enzyme results in accumulation of L-alanine, L-asparagine, L-histidine, indoleacetic acid, L-isoleucine, L-leucine, L-phenylalanine, L-serine, L-threonine, L-tryptophan, L-valine, and L-tyrosine in urine. Symptoms include pellagra, psychosis, ataxia, and mental retardation. Treatment includes nicotinamide.

Guanidinoacetate Methyltransferase Deficiency (Creatine-Deficiency-Syndrome) is a rare autosomal recessive disease caused by a mutation in the GAMT gene which codes for guanidinoacetate N-methyltransferase. A deficiency in this enzyme results in accumulation of 3-methylglutaconic acid in urine; guanidoacetic acid in urine and serum. Decreased concentrations of creatine are found in serum and urine; and creatinine in plasma, spinal fluid, and urine. Symptoms, which present at birth, include failure to thrive, mental and motor retardation, hyoptonia, and seizures. Treatment includes arginine-restricted diet, sodium benzoate, and L-ornithine hydrochlorate.

Glycerol Kinase Deficiency (Hyperglycerolemia; Glyceroluria; GK Deficiency; GKD) is a rare metabolic disease caused by a deficiency in the GK gene which codes for glycerol kinase. A deficiency in this enzyme results in accumulation of glycerol in urine and serum. Symptoms include cryptorchism, trabismus, myopathy, lethargy, and vomiting. Treatment includes corticosteroids and acute glucose infusion.

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.

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.