Genetic Testing for PND's*

Diagnosis of PND's can be made in different ways. For the dopamine/serotonin related diseases an initial screening of the cerebral spinal fluid (CSF) for dopamine and serotonin metabolites is recommended. For some dopamine and serotonin related diseases diagnosis can be confirmed by different tests which may include enzyme testing of the blood or skin fibroblasts or a phenylalanine loading challenge**.

For specific diagnostic information please refer to the disease section on this site.

Genetic testing however provides the most accurate confirmation of a disease and can be extremely helpful. Genetic testing is available for all PND's and requires a sample of blood for isolation of DNA. Often there are multiple and/or unknown mutations that exist and this can make a genetic confirmation difficult.

Geneticists use maps to describe the location of a particular gene on a chromosome. For more information about how genes are mapped go to www.ghr.nlm.nih.gov

For information about specific genetic testing and where a test can be obtained go to GENETESTS www.genetest.org.

GeneTests is a publicly funded medical genetics information resource developed for healthcare providers, and researchers, available at no cost to all interested persons. For access key in Gene Review and then the name of the specific disease.

Genetic Diagnostic Testing

Succinic Semialdehyde Dehydrogenase Deficiency - inherited as an autosomal recessive disorder. ALDH5A1 is the only gene currently known to be associated with SSADH Deficiency.
Gene map locus 6p22.

Aromatic L-Amino Acid Decarboxylase Deficiency - inherited as an autosomal recessive disorder.
Gene map locus 7p11.

Tyrosine Hydroxylase (TH) Deficiency - inherited as an autosomal recessive disorder.
Gene map locus 11p15.5.

Dominant Guanosine Triphosphate Cyclohydrolase I Deficiency - inherited as an autosomal dominant disorder.
Gene map locus 14q22.1-q22.2.

Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency - inherited as an autosomal recessive disorder. Some forms of recessive GTPCH deficiency (normally those with two different mutations) can only be initially detected via testing of CSF for dopamine and serotonin metabolites.
Gene map locus 14q22.1-q22.2.

Sepiapterin Reductase Deficiency - inherited as an autosomal recessive disorder.
Gene map locus 2p14-p12.

Carrier Testing

Succinic Semialdehyde Dehydrogenase Deficiency - carrier testing is available using molecular genetic analyses on a clinical basis once the mutations in the proband have been identified.

Aromatic L-Amino Acid Decarboxylase Deficiency - carrier testing is easily performed by measurement of AADC enzyme activity in plasma. This requires collection of two ml's of blood, separation of plasma and freezing the sample at -70oC until testing.

Tyrosine Hydroxylase Deficiency - there is no simple means of testing for TH carriers. If a family member has been shown to have TH deficiency and sequencing of the TH gene in the affected proband has located the pathogenic mutation(s), then it is possible to sequence the putative carriers DNA and determine if they carry a mutation or not. This test requires collection of whole blood (5 ml) for extraction of DNA for sequencing.