Mabry Syndrome

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This disorder is caused by problems in either the PIGV, PIGO, or PGAP2 gene. The genes are needed to produce a molecule called a GPI anchor. This molecule attaches itself to different types of protein such as alkaline phosphatase and binds them to the surface of cell membranes. A problem in either of the above genes means that the anchor is incomplete and therefore proteins are not attached to cells. As a result, the level of alkaline phosphatase is increased in the blood, this is known as hyperphosphatasia. The type of alkaline phosphatase that is raised is called non-specific tissue alkaline phosphatase and this is a key finding used to diagnose Mabry Syndrome.

The most common cause of this disorder is problems in the PIGV gene. A small number of cases are caused by problems in either the PIGO or PGAP2 gene. There are a few cases in which the cause is unknown.

Approximately 20 cases of this disorder have been reported.

Signs and symptoms of Mabry Syndrome vary greatly. Some may only have one or two symptoms. In some cases, symptoms may only include intellectual disability and Hyperphosphatasia. Hyperphosphatasia itself does not have any physical symptoms.

Signs and symptoms which may occur include:

• Delays in mental and motor developmental milestones affecting skills such as sitting, crawling, standing, walking
• Moderate to severe intellectual disability
• Characteristic facial features including wide-set eyes, widened opening of the eyes, a broad nasal bridge and rounded nose, thin lips and downturned corners of the mouth.
• Low muscle tone (hypotonia)
• Recurrent seizures (epilepsy)
• Shortened bones at the ends of the fingers
• Underdeveloped fingernails
• Cupped ears
• Hearing loss
• Narrowing or blockage of the anus

Hirschsprung Disease; a condition that is present from birth and causes a blockage of the intestine and bowels resulting in severe constipation.

This disorder is likely to be upon identification of the following three symptoms:

• developmental disability
• seizures
• hyperphosphatasia

Characteristic facial features can also contribute towards diagnosis. Diagnosis can be confirmed following genetic testing.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.

In most cases, this is an inherited condition. However, sometimes it can occur sporadically. There is nothing that could have been done to prevent it.

Everyone has a pair of genes that are needed to make the GPI anchor. In children with Mabry Syndrome, neither of these genes works correctly. These children inherit one non-working gene from each parent.

Parents of children with Mabry Syndrome are carriers of the condition. Carriers do not have the disorder because the other gene of this pair is working correctly.

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

• 25% chance (1 in 4) of Mabry Syndrome
• 50% chance (1 in 2) for the baby to be a carrier of Mabry Syndrome
• 25% chance (1 in 4) for the baby to have two working genes and neither have Mabry Syndrome or be a carrier

References are available on request. Please contact us on 0800 652 3181 or by emailing contact@metabolicsupport.org.

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.