Sulphite Oxidase Deficiency

What is Sulphite Oxidase Deficiency?

Sulphite oxidase deficiency is an extremely rare inherited disease in which incorrect ‘metabolism’ or processing of the amino acids methionine and cysteine leads to accumulation of their by-products in the blood and tissues. These products cause severe mental retardation, physical deformities and progressive brain damage.

Amino acids such as methionine and cysteine are the building blocks of proteins. After eating proteins, the body breaks them down into amino acids. Animal proteins include dairy products, meat, eggs and fish. Proteins are also found in plants including soy, legumes, grains and nuts. The body uses the amino acids to make its own proteins essential for life – for example enzymes; structural proteins in muscles, hair, skin, cells and cartilage; proteins that generate movement in muscles; or those involved in cell functioning or immune responses. In periods of fasting or illness, the body often switches to use its own proteins, and stored fats, to generate energy. Methionine is present in both animal and plant proteins, especially sesame seeds, nuts, spinach, mushrooms, broccoli, potatoes, fish and meat. Cysteine is found in most high-protein foods including meat, milk, eggs, red peppers, onions, broccoli and oats.

Sulphite oxidase is an enzyme that resides in the mitochondria, the energy-producing machinery inside cells. The enzyme is required for proper metabolism of methionine and cysteine.

How common is sulphite oxidase deficiency?

Only around 50 cases of sulphite oxidase deficiency have been reported worldwide.
Both males and females have been affected in equal proportions.

What causes sulphite oxidase deficiency?

Sulphite oxidase deficiency is linked to a genetic mutation that causes a defect either in the sulphite oxidase enzyme itself or, more commonly, in the helper or ‘co-factor’ molecule known as molybdenum co-factor. Since methionine and cysteine cannot be metabolised correctly, toxic by-products are left within the body that wreak havoc on Sulphite oxidase deficiency is linked to a genetic mutation that causes a defect either in the sulphite oxidase enzyme itself or, more commonly, in the helper or ‘co-factor’ molecule known as molybdenum co-factor. Since methionine and cysteine cannot be metabolised correctly, toxic by-products are left within the body that wreak havoc on the central nervous system. The exact mechanism by which this damage occurs has not been defined.

Sulphite oxidase deficiency is a recessively inherited genetic disorder, meaning that a child would only have the condition if both parents ‘carry’ the genetic mutation. Genes are arranged in structures called chromosomes that contain two strings or ‘alleles’. Offspring inherit one allele from their father and one from their mother. Carrying one copy of the mutated gene does not affect health, but when two mutated copies come together, the linked enzyme is deficient either in quantity or effect and the disease is expressed. For each and every pregnancy, there is a 1 in 4 chance of two carriers of the genetic mutation having a child with the disease. 

What are the symptoms and signs of sulphite oxidase deficiency?

Symptoms and signs of sulphite oxidase deficiency usually appear in infancy. In this scenario, severe seizures begin in the first days or weeks of life, which are hard to treat. The infant shows feeding problems, abnormal muscle tone, muscle twitching and signs of severe brain damage. Abnormal tightening of the muscles or ‘spasticity’ in the spinal column pulls the spine, neck and head into a backward arch shape. The prognosis is extremely poor, and many infants with sulphite oxidase deficiency lose their life to the disease. For those who survive, severe mental retardation is common. Furthermore, the eyes may show a lack of response to light and the lens of the eye can become dislocated.

In some individuals, the disease presents later in infancy or childhood. Individuals with this later-onset variation of sulphite oxidase deficiency potentially show less severe symptoms. For example, they may lose previously acquired milestones, such as being able to walk unaided or grasp objects, or can develop movement disorders. The outcome is thought to be better in this variant, although more research is needed to properly define the disease.

Children and infants with sulphite oxidase deficiency tend to have characteristic facial features comprising a narrow face diameter with deep-set eyes.

How is sulphite oxidase deficiency diagnosed?

Blood and urine tests are normally the first investigations to be carried out when a diagnosis of sulphite oxidase deficiency is suspected. The most indicative are blood and urine tests to detect methionine and cysteine metabolites and a urine test to detect sulphite. Assessment of enzyme and co-factor levels is also revealing. Computed tomography (CT) and magnetic resonance imaging (MRI) can help evaluate the degree and type of brain damage.

How is sulphite oxidase deficiency treated?

Since there are so few cases of sulphite oxidase deficiency, little is know about how best to treat the condition.

For those with late-presenting disease, there may be some benefit from a diet that restricts protein in general and methionine and cysteine specifically. The diet needs to be continued indefinitely and must be initiated only after consultation with a dietician. As with any restrictive diet, it is important to ensure optimal nutrition. While natural protein intake is limited, a formula free of methionine and cysteine is prescribed. The specially formulated powder is designed to meet the nutritional needs of children at different ages. It contains a balanced mix of essential and non-essential amino acids, vitamins, minerals and carbohydrates to avoid malnutrition of other amino acids and to sustain normal growth and development in children. Several low-protein food products are also available.

Various drug treatments have been tried, although no definitive treatment can be recommended. For example, trimethylglycine or ‘betaine’ can be prescribed as this helps to metabolise cysteine, thus reducing levels of this amino acid in the body. However, this treatment is not suitable for infants. Similarly, thiamine (vitamin B1) supplementation may also be beneficial since this vitamin is low in sulphite oxidase deficiency.