Browsing Pathways

Galactokinase deficiency also called Galactosemia type II, is a rare inborn error of metabolism (IEM) and an autosomal recessive disorder of galactokinase caused by a mutation in the GALK1 gene on chromosome 17q24. Galactokinase uses 1 ATP to catalyse the phosphorylation of α-D-galactose to galactose 1-phosphate and catalyses β-D-galactose to glucose 1-phosphate. Symptoms include cataract formation in children who are exposed to lactose in their diets. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens. Treatment includes immediately removing lactose from patient’s diet, however symptoms such as delayed speech, cognitive learning and motor skills can still be present.

Galactosemia III also called GALE deficiency or UDP-Galactose-4-Epimerase deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by either a homozygous or compound heterozygous mutation in the UDP-galactose-4-epimerase (GALE) gene. GALE catalyses the reversible conversion of UDP-galactose to UDP-glucose in galactose metabolism. Symptoms are similar to classic galactosemia, including jaundice, vomiting, hypotonia, failure to thrive, hepatomegaly, moderate generalized amino aciduria and marked galactosuria. Treatment usually includes galactose restricted diets instead of galactose free diets in the management of this disorder because unlike patients with galactokinase deficiency and classic galactosemia, patients with galactose epimerase deficiency cannot utilize the endogenous pathway for synthesis of UDP-galactose. This makes patients dependent on exogenous galactose.

Tyrosine Hydroxylase (TH) Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of catecholamines pathways. The disorder is caused by defects in the Tyrosine hydroxylase (TH) gene which encodes for the enzyme tyrosine hydroxylase. This enzyme is part of the production of catecholamines such as dopamine, norepinephrine and epinephrine are all essential for normal nervous system function. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Norepinephrine and epinephrine are involved in the autonomic nervous system. Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. Symptoms of the disorder include abnormal movements, autonomic dysfunction, and other neurological problems. Treatments can include the administration of levodopa; however patient responses can vary greatly. The frequency of Tyrosine Hydroxylase Deficiency is unknown.

Dopamine beta-hydroxylase deficiency (or norepinephrine deficiency) is caused by mutation in the gene encoding dopamine beta-hydroxylase. Clinical features include orthostatic hypotension, ptosis, nasal stuffiness, and a neonatal history of delayed eye opening. Noradrenaline and adrenaline are generally not detectable in plasma, urine, and cerebrospinal fluid, but dopamine is increased 7- to 12-fold in plasma, 4-fold in urine, and 20-fold in CSF. Treatment with dihydroxyphenylserine has been shown to reduce symptoms and signs of postural hypotension and increase plasma levels of noradrenaline.

Metcaptolactate-cysteine disulfiduria (MCDU) is an autosomal disorder that leads to the loss of function of the enzyme mercaptopyruvate sulfurtransferase. The condition is characterized by the urinary excretion of large amounts of a sulfur-containing amino acid, which is beta-mercaptolactate-cysteine disulfide. Patients exhibit a low IQ, grand mal seizures, flattened nasal bridge, and an excessively arched palate.

5-Oxoprolinase deficiency, also called OPLAHD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of glutathione metabolism caused by a defective 5-oxoprolinase. 5-Oxoprolinase catalyzes the conversion of 5-oxoproline into glutamate which is an important neurotransmitter. This disorder is characterized by a large accumulation of 5-oxoproline in the urine. Symptoms of the disorder include enterocolitis, mental retardation, kidney stone formation, and hypoglycemia. 5-Oxoprolinase deficiency has been reported in approximately 8 people.

Gamma-glutamyltranspeptidase deficiency, characterized by glutathionemia and glutathionuria, is an autosomal recessive disorder of glutathione metabolism caused by a defective gamma-glutamyl transpeptidase (GGT). GGT transfers glutamyl moieties to acceptor molecules such as amino acids and peptides. This disorder is characterized by a large accumulation of glutathione in the urine. Symptoms of the disorder include easy bruising, asthma, and mild mental retardation.

Malonyl CoA decarboxylase deficiency, also claled MCD deficiency, is a rare inborn error of fatty acid metabolism and autosomal-recessive metabolic disorder, which is caused by a defective mitochondrial malonyl CoA decarboxylase due to reduced activity. Mitochondrial malonyl CoA decarboxylase catalyzes the conversion of intramitochondrial malonyl CoA to acetyl CoA, which is a key product that involve in many biochemical reactions. This disorder is characterized by a large accumulation of methylmalonic acid in the mitochondrial. Symptoms of the disorder include hypotonia (i.e. weak muscle tone), hypoglycemia (i.e. low blood sugar), diarrhea, seizures and vomiting. The Malonyl CoA decarboxylase deficiency is an extremely rare genetic disease happened in early childhood, which only less than 30 cases have been reported. There is currently no cure for Malonyl CoA decarboxylase deficiency, treatment involves managing the disorder's symptoms.

Infantile hypophosphatasia, also called I-HPP, is a severe, rare and fatal metabolic bone disease and an inborn error of metabolism. I-HPP is caused by a defective alkaline phosphatase, tissue-nonspecific isozyme, which catalyzes the conversion of pyridoxal 5'-phosphate into pyridoxal and conversion of pyridoxamine 5'-phosphate to pyridoxamine. Both products are important for later metabolism. Early symptoms of the disorder include poor feeding, irritability, hypotonia (state of low muscle tone), failure to thrive and seizures.. Treatment with enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase is very effective. It is a very rare genetic disease happened in infant, with 90 cases have been reported to date.

Guanidinoacetate methyltransferase deficiency, also called GAMT deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of creatine metabolism caused by a defective guanidinoacetate methyltransferase (GAMT). GAMT catalyzes the conversion of guanidinoacetate into creatine which is used by creatine kinase to resynthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP). This disease is characterized by a large accumulation of guanidinoacetate and a decrease in creatine in the blood and urine. Symptoms of the disease include developmental delay, hypotonia, and seizures. Treatment with creatine supplementation is very effective. It is estimated that GAMT deficiency affects 1 in 250 000 individuals.