KRYPTOPYRROLURIA, COULD IT BE KPU?

Kryptopyrroluria (KPU) is thought to be one of the most under-recognized conditions in the UK. Some estimates suggest the incidence of KPU to be as high as 80% in autism and between 40% and 70% in those with learning difficulties, ADHD, depression and bipolar disorders.

What is KPU (HPU)?

KPU, also known as HPU, (Haemopyrroluria), is a condition where pyrrole, a key component of haem, (the red pigment in blood) is overproduced in the liver and bone marrow. Normally excess pyrrole is excreted in bile pigments via the stool. However, if there is an unusually high buildup of pyrrole, it is excreted via the urine. This buildup can cause a host of symptoms, including; digestive, hormonal and connective tissue disorders, oxidative stress as well as mental, emotional and neurological problems, very similar to those experienced in autism.

There appears to be a genetic component to this condition but there is also a strong correlation between levels of stress and the severity of symptoms. It has been suggested that the condition can also be induced by chronic infection, and severe childhood trauma and that KPU and candida overgrowth are inter-linked and promote each other’s development.

What is the mechanism of KPU?

Pyrroles bind to or inhibit the nutrients; zinc, vitamin B6, manganese, biotin, gamma-linolenic acid and other B vitamins, especially vitamins B2, B3 and B5, and lead to significant deficiencies of these substances in the body.

Considering the fundamental parts these nutrients play in the immune system, the methylation cycle and in virtually every single body function it is easy to see how symptoms associated with KPU can develop.

Zinc

Zinc is vital for the functionality of more than 300 enzymes, for the stabilization of DNA and gene expression. Its deficiency can result in a significantly compromised immune system, which is so often the case in autism. As DR Klinghardt puts it “white blood cells without zinc are like an army without bullets”.

Zinc deficiency can also cause many other symptoms such as; depression, lethargy, poor wound healing, picky eating, delayed puberty, and even dyslexia.

Vitamin B6 deficiency in Kryptopyrroluria

Vitamin B6 deficiency is common amongst those with KPU and can result in a host of symptoms such as anxiety, insomnia, irritability, and muscle weakness. The first step in haem synthesis is B6 dependent – without haem, haemoglobin synthesis is compromised, and subsequently so is oxygen transport. Given the first step of haem synthesis occurs in the mitochondria (responsible for energy production), there is a strong connection between KPU and mitochondrial disorders.

Depression of heam production can lead to serious metabolic defects and may explain why in some cases anaemia is persistent and does not respond to iron supplementation. B6 plays a significant part in the methylation cycle, the metabolism of amino acids and the synthesis of neurotransmitters.

Often in organic acid tests, those with KPU, have raised levels of B6 dependent metabolites of branch chain amino acids (BCAA); leucine, isoleucine and valine, as well as high Citrulline and elevated ammonia levels. B6 is necessary for the conversion of Glutamate to GABA (gamma-Aminobutyric acid). Many children with autism are sensitive to glutamate levels. Glutamate is an excitatory neurotransmitter essential for learning and GABA is a calming neurotransmitter, essential for speech.

In Kryptopyrroluria this conversion is disrupted due partly to B6 deficiency and can lead to excessively high glutamate levels, which can deplete levels of glutathione, a major antioxidant, essential for healthy detoxification. The knock on effect from lowered glutathione levels is the tendency for a compromised gut lining.

Biotin

Biotin plays a key role in fat and sugar metabolism. The physical symptoms of biotin deficiency tend to include; hair loss, brittle nails and dry hair and skin and scaly red rash around the eyes, nose, and genital area. Neurological symptoms can include, lethargy, depression, numbness and tingling sensation in the limbs, tremors, and in some cases seizures.

Manganese

Manganese helps the body form connective tissue, and its deficiency has been associated with joint pain and inflammation. Manganese also plays a key role in the metabolism of carbohydrates, fat, amino acids and cholesterol and the production of thyroid hormone. Supplementation with manganese in KPU is a double-edged sword, however.

According to DR Klinghardt, almost 80% of those with Lyme disease also have KPU. Scientists have discovered that the pathogen that causes Lyme disease, unlike other known organisms – can exist without iron and instead, the bacteria substitute manganese and hides from the immune system in stealth mode. Before supplementing with therapeutic levels of manganese it is important to rule out Lyme disease (Read more in our article – What’s Lyme got to do with it?).

Gamma Linolenic Acid (GLA)

GLA is an important constituent of the cell membrane and its deficiency can affect the function of white blood cells, especially leukocytes. Other symptoms can be dry, itchy, scaly skin, dandruff, gastrointestinal disturbances and food intolerances.

KPU Test – Testing for Kryptopyrroluria

KPU can be easily tested through urine. The test is not expensive but it’s easy to get false negatives, given its extreme sensitivity to light, temperature and oxygen. Choosing the right laboratory to carry out the test is paramount.

To ensure accuracy it’s very important to remove all supplements, especially any containing zinc, biotin and vitamin B6 for 4 to 7 days before completing the test. Additionally, The sample needs to be tested within 24 hours of collection. Biovis Diagnostik in Germany has been consistent with its reporting of KPU tests and is a good choice.

At Brainstorm Health we often test our patients for KPU as part of our standard process. Biomedical testing is an important step in our approach and methodology – see how we work with you and your child.

KPU diet – Kryptopyrroluria food sources and supplements

A holistic strategy to support KPU needs to include; replenishing lost nutrients, detoxification support, and targeted strategies for removing chronic infections, whilst supporting the gastrointestinal tract, the mitochondria and the immune system. Depleted vitamin B6 and zinc can have a tremendous impact on the detoxification pathways. Replenishing zinc and b6 levels can significantly increase the rate of detoxification and release a large number of toxins into the system.

It is extremely important to support the detoxification pathway fully and have in place a strategy to remove the toxic load. Intake of food sources of zinc, B6, manganese, biotin and GLA would also be helpful – please see table below for a list of foods rich in these nutrients.

KPU disease symptoms

• Physical appearance: Pale, sallow skin, pale lips, pruritis either in certain areas or all over (anal pruritis is particularly prevalent in children); light intolerance, rash in sunlight, yellowish-brown pigmentation after being in the sun, slight puffiness of the face, especially around the cheeks and eyes. Dark rings around the eyes, eyes sunk deep into their sockets; soft gums; striae on the skin similar to stretch marks; white spots on the nails (leukodynia), sometimes hair loss, acne, eczema and dandruff; poor tooth enamel
• Neurological issues, often labelled psychiatric: Memory and concentration difficulties, problems with short-term memory, “brain fog”, poor dream recall, low mood, fear, panic attacks, misophonia, withdrawal from social activities, hallucinations, apparent schizophrenia/psychosis, ADHD
• Impaired energy production: Fatigue, may be severe
• Detoxification issues, resulting in intolerance to medications and chemicals (MCS)
• Thyroid disorders: Hypothyroidism, Hashimoto’s thyroiditis
• Immune disorders, particularly bronchial infections, cystitis and urinary infections, sinusitis particularly in children
• Musculoskeletal symptoms: Hypermobility, pelvic instability, weak muscles. Often muscle and joint pain (due to myoglobin being affected, because it has a haem group)
• Gastrointestinal disorders: Bloating, pain, nausea, especially in the morning. Alternating diarrhoea and constipation, halitosis, aversion to meat (the conversion of muscle protein to own protein is B6-dependent)
• Blood sugar disorders: Hypoglycaemia (gluconeogenesis is B6-dependent); diabetes type II
• Methylation issues, hyperhomocysteinaemia

Source: Joachim Strienz, “Leben mit KPU – Kryptopyrrolurie” (Living with KPU – Kryptopyrroluria, only available in German), and KPU, Kryptopyrrolurie: eine haeufige aber vergessene Stoffwechselstoerung by Kyra Hoffmann, and Sascha Kauffmann

Summary

Given the number of key nutrients that are depleted in a single condition such as KPU, the implications on health can be vast and significant. Many of those with a long and complicated history of chronic illness, neurological conditions, including autism, should consider testing for KPU.

If you read this and think your child might be suffering from KPU, then please get in contact with us to find out how we can help. We also suggest reading more on our website, especially; How we work, Brainstorm Health Programme, and our approach to Nutritional Therapy. We have a dedicated team ready to help you and your child!

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Featured article in the Autism Eye Magazine December 2015. Written by Stella Chadwick.