There are around 7000 different variations of rare genetic disorders that plague a significant percentage of the global population. Approximately 1 out of every 10 American is known to suffer from rare genetic disorder. Among the many genetic disorders that affect children all over the globe, Deficiency of Interleukin 1 Receptor Antagonist or DIRA is a rare occurrence that affects children at the very inception of their life.
What is Deficiency of Interleukin 1 Receptor Antagonist?
Deficiency of the Interleukin 1 receptor antagonist can be defined as an extremely rare genetic condition that manifests itself in the first few days of human life. It is a rare genetic auto inflammatory syndrome with high resemblance to severe cases of acute systemic infection or a contagion of the bone. A relatively new discovery, Deficiency of the Interleukin 1 receptor antagonist is caused by the mutation of the IL1RN, which is the gene which encodes the interleukin 1 receptor antagonist. Affecting new born babies within the age group of 0-2 weeks, Deficiency of the Interleukin 1 receptor antagonist can be treated with early diagnosis and intervention failing in which can lead to multiple organ failures.
Signs and Symptoms of Deficiency of Interleukin 1 Receptor Antagonist
Deficiency of Interleukin 1 receptor antagonist or DIRA manifests itself within a couple of weeks after birth. The signs and symptoms of the condition in the first few days after birth include-
- Swelling of the joints
- Fetal distress
- Hepatosplenomegaly or the enlargement of the liver and spleen
- Pustular rash
- Oral lesions
- Painful movement.
It is common for all the affected children with Deficiency of the Interleukin 1 receptor antagonist to develop pustular rash; in some cases it might be in a scattered form while in others, the eruptions might be severe resembling generalized pustular psoriasis. Certain manifestations have also been noted at the skin or mucosal level, viz.-
- Oral ulcers
- Changes in the nail such as, separation of the nails from the nail beds; nail psoriasis and the like.
- Pyoderma gangrenosum.
The children affected with Deficiency of Interleukin 1 receptor antagonist also suffer from inflamed joints, making movement painful. Along with the above mentioned signs and symptoms, there are certain other signs and symptoms that have been found to be manifested in the children including-
- Cerebral vasculitis or the inflammation of the blood vessels in the brain
- Hypotonia or weak muscle tone
- Absence of significant growth
- Pulmonary haemosiderosis with progressive interstitial fibrosis.
Deficiency of Interleukin 1 receptor antagonist can result in multiple organ failure and even death if left without appropriate medical attention.
Causes of Deficiency of Interleukin 1 Receptor Antagonist
Deficiency of Interleukin 1 receptor antagonist or DIRA is caused by the homozygous mutations in the IL1RN gene or a large obliteration affecting the mentioned gene and other such genes belonging to the IL family of genes on chromosome 2. The protein IL-1 is encoded by the IL1RN gene and the inflammatory actions of the IL-1 are generally controlled by the IL-1Ra. The mutation of IL1RN leads to loss of control in the systemic inflammation caused by the IL-1 in children. Consequently, these mutations lead to blockage in the secretion of the protein, thereby, exposing the cells to unopposed activity of interleukin 1. This in turn leads to periostotis, sterile multifocal osteomyelitis, and pustulosis from the very birth of the child. The rate at which children are affected by Deficiency of Interleukin 1 receptor antagonist varies according to the region- around 0.2% of the cases have been reported in Newfoundland and 1.3% in Puerto Rica.
Diagnosis of Deficiency of Interleukin 1 Receptor Antagonist
Physiologists are likely to conduct a number of examinations to confirm that the cause of the manifestations of Deficiency of Interleukin 1 receptor antagonist or DIRA in the new born which includes-
- Skin and Bone Biopsy: While evidences of epidermal acanthosis, thrombosis, hyperkeratosis, and heavy neutrophil infiltrate of the dermis, formation of pustules along the hair follicles and epidermal neutrophilic pustules are seen in the skin biopsy, the biopsy of the bone reveals sclerosis, fibrosis, purulent osteomyelitis and vasculitis in the neighboring fat and connective tissue.
- Blood Tests: The blood tests of the child affected with Deficiency of Interleukin 1 receptor antagonist or DIRA are likely to show an increase in the CRP or C-reactive protein and ESR or Erythrocyte Sedimentation Rate.
- Cerebral MRI: The evidences of Cerebral Vasculitis are likely to be noted in the Cerebral MRI of the affected child.
- DNA Analysis for the Diagnosis of Deficiency of Interleukin 1 Receptor Antagonist: The DNA Analysis of the affected child is likely to show the obliteration of a large gene including IL1RN that leads to the absence of the functional interleukin 1 receptor.
- X-Rays: Swelling of the ribs, periosteal elevation, heterotopic ossification, multifocal osteolytic lesions are seen in the X-Rays of the affected child.
Treatment of Deficiency of Interleukin 1 Receptor Antagonist
Children affected with Deficiency of Interleukin 1 receptor antagonist can be treated effectively with the help of anakinra. This can be defined as a biological substitute for the protein which the children lack and is a recombinant state of interleuin-1 receptor antagonist. Regular subcutaneous administration of anakinra resulted in normalization of the symptoms of the skin and bone within months. While the affected children have shown remarkable and long lasting improvements, the cessation of the treatment have shown a relapse of the symptoms within 36 hours. Although, there are certain other side-effects of the treatment such as itchiness and swelling of the skin and the appearance of rashes, these are generally tolerable and the treatment is likely to be successful.
Who are Affected by Deficiency of Interleukin 1 Receptor Antagonist?
Deficiency of Interleukin 1 receptor antagonist or DIRA affects a very small fraction of children with the reported cases being situated in Puerto Rico, Newfoundland, Lebanon and The Netherlands. It affects children at the very birth or in the couple of weeks post-birth. The condition is genetically autosomal recessive in nature, which means that a child of two carrier parents has a 25% chance of being affected by Deficiency of Interleukin 1 Receptor Antagonist.
Deficiency of Interleukin 1 receptor antagonist or DIRA is a rare genetic disorder affecting children right at the birth or in the first few days after their birth. However, this condition can be treated with the regular administration of the anakinra failing to do which can have fatal consequences.