Low BH4 Disorders

Disorders That Are a Direct Result of Low BH4

A variety of mutations in the genes involved in the producuction of BH4 (GCH1, PTS and SPR), can result in BH4 deficiency disorders. Additionally, mutation in genes involved in the recycling BH2 to BH4 (PCBD1, QDPR, MTHFR [A1298C variant] and DHFR), can also result in BH4 deficiency disorders.

There are primarily two health disorders resulting from low BH4 levels, and they each can vary greatly in sevirity, from person to person, from mild to life-threatening. These two disorders are often referred to by other names, many of which are listed here. Don't be overwhelmed by all the "other" names, they are here simply as a reference.

Dopa-Responsive Dystonia (DRD)

Dopa-Responsive Dystonia (DRD) is a disorder that involves involuntary muscle contractions, movements and tremors. DRD sysmptoms can range from mild to severe. It is referred to a "Dopa-Responsive", because symptoms typicaaly greatly improve with life-long treatment of a medication called L-Dopa. Over time, many people with this condition develop movements abnormailites that are referred to as parkinsonism. Though it may look similar to Parkinson's, it is not. DRD is likely underdiagnosed, because the condition may not be identified in people with mild symptoms.

Other names for Dopa-Responsive Dystonia (DRD):

  • Dystonia 5, Dopa-Responsive Type
  • Hereditary progressive dystonia with marked diurnal fluctuation

When DRD is caused by mutations in the GCH1, it can also be referred to as:

Autosomal dominant dopa-responsive dystonia
Autosomal dominant Segawa syndrome
GTP Cyclohydrolase 1 Deficiency (GTPCH)
GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia
GTP cyclohydrolase I deficiency (GTPCH deficiency)
GTP Cyclohydrolase 1-Related Disorders
GTPCH1-deficient dopa-responsive dystonia

When DRD is caused by mutations in the PTS gene, it can also be referred to as:

6-Pyruvoyltetrahydropterin Synthase Deficiency
6-alpha Pyruvoyltetrahydropterin Synthase Deficiency
Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency
http://en.wikipedia.org/wiki/6-Pyruvoyltetrahydropterin_synthase_deficiency
http://www.ncbi.nlm.nih.gov/pubmed/15984017
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=13

When DRD is caused by mutations in the SPR gene, it can also be referred to as:

Dopa-Responsive Dystonia Due to Sepiapterin Reductase Deficiency
Sepiapterin Reductase Deficiency

Tetrahydrobiopterin Deficiency

Other names for Tetrahydrobiopterin Deficiency:

When DRD is caused by mutations in the DHFR gene, leading to a BH4 deficiency, it can also be referred to as:

BH4-Deficient Hyperphenylalaninemia C (Caused by mutations in the QDPR gene, resulting in a Dihydropteridine Reductase Deficiency (DHPR deficiency).

When DRD is caused by mutations in the DHFR gene, leading to a BH4 deficiency, it can also be referred to as:

BH4-Deficient Hyperphenylalaninemia D ( Caused by mutations in the PCBD1 gene, resulting in a Dihydropteridine Reductase Deficiency (PCBD Deficiency).