Pyrroluria: A Commonly Missed Diagnosis
What if large numbers of people were affected by a common syndrome that makes them susceptible to a wide range of diseases? What if this syndrome usually responds rapidly to a simple inexpensive treatment? What if this syndrome was largely unknown to the medical profession?
Well, such a syndrome does exist and it is called pyrroluria (sometimes kryptopyrroluria or pyrrole disorder). It is a metabolic disorder caused by abnormal metabolism of pyrroles which are formed from the breakdown of heme (or haem) in haemoglobin. This, in turn, causes abnormal excretion of pyrroles into the urine.
Pyrroles are produced in enormous quantities by the body. The breakdown of a single red blood cell can create four billion pyrroles. Normally pyrroles are converted to a water-soluble metabolite excreted in the urine. In krytopyrroluria, due to a faulty enzyme it is converted to haemopyrrole and excreted in the urine.
This leads to a major problem. Haemopyrrole forms a complex with vitamin B6 which is then excreted. This complex with B6 also chelates zinc which is also excreted, creating a chronic deficiency of both. Other nutrients including manganese, copper, vitamins B2 and B12 can also become depleted.
The cause can be genetic but other factors including poor diet, physical and mental stress exacerbate symptoms and block compensatory pathways.
The reason this syndrome is important is because it is so common. It is most frequently associated with mental health conditions. It is more common than usual in schizophrenia (at least 30%), anxiety and depression (12-40%), manic depression (45-50%), autism (46-80%), learning disorders (40-47%) alcoholism (25%), substance abuse (75%), ADHD (40-70%) and affects 42% of psychiatric patients. In can occur in genetic conditions including Down’s syndrome (71%). It affects about 10% of normal people.
Practitioners have noted it is frequently found in chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, thyroid disease and epilepsy (44%). It is far commoner in women (possibly a 10:1 ratio) and very common in cases of heavy metal toxicity (zinc normally protects against this). Pyrroluria may run in families (there was a recorded case of a family of 15 who all suffered from it). There may be a family history of mental illness and it is far more common in all-girl families.
Although double-blind trials are lacking, clinical observations spanning five decades have confirmed the features of this syndrome.
The syndrome is important to recognise but unfortunately diagnosis is rarely considered. Without diagnosis, other treatments may only lead to partial improvement. Correct diagnosis may not only relieve the condition but have multiple added benefits (see consequences below). In addition, correct diagnosis may lead to benefits to other members of the family subsequently diagnosed.
Another reason it is important is that it is very amenable to treatment. Correcting the deficiencies typically leads to rapid improvement.
The consequences of krytopyrroluria are major. This causes disruption of many of the body’s most critical functions. These include reduced ability to produce nitric oxide synthase, decreasing nitric oxide, (arguably the most important anticoagulant in the body), lowered ability to breakdown homocysteine, decreased ability to detoxify, reduced capability for apoptosis and decreased mitochondrial function.
Symptoms of pyroluria include fatigue, frequent infections, insomnia, poor memory, splenic pain, itching in sunlight, aching knees, morning nausea, a tendency to hypoglycaemia, seizures and lack of dream recall. Cognitive symptoms are common including reduced short-term memory, poor concentration and brain fog. Other symptoms anxiety, depression, poor sleep and mood swings. Irregular periods can affect girls, and relative impotence can affect boys. They can have bad breath, white spots on their fingernails, a strange body odour and poor tolerance for drugs and alcohol. Worsening with Omega 3 fats but improvement with Omega 6s such as evening primrose can be a clue to this disorder. Blood tests may show eosinophilia, lymphocytosis, raised bilirubin and low immunoglobulin A.
A urine test for will detect the excess and abnormal pyrroles, usually HPA (hydroxyhemopyrrole-2-one). It has also been caused mauve factor because of the mauve appearance of the urine on chromatograms. This test is not available on the NHS but can be done through specialised laboratories. The Academy of Nutritional Medicine can arrange this test (try info@aonm.org).
Treatment is with zinc and vitamin B6 and sometimes other nutrients. A relatively high dose is usually needed (usually Vitamin B6: 100-800mg daily and zinc: 25 to 100mg daily) and long-term treatment will usually be needed.
