Rare Cases

السلام عليكم ورحمة الله وبركاته
في هذا الموضوع سنتناول حالات لأمراض نادرة تم اكتشاف مصابين بها في مستشفى الجامعة الأردنية / قسم الأطفال .
سيتم ذكر الحالة باختصار ومن ثم وضع معلومات من الإنترنت عنها .

Congenital insensitivity to pain with anhidrosis








Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare inherited disorder of the nervous system which prevents the sensation of pain, heat, and cold. A person with CIPA cannot feel pain or differentiate even extreme temperatures. "Anhidrosis" means the body does not sweat, and "congenital" means that the condition is present from birth. Many scientists believe that this condition is both androphenic and supplementary to the thyroid system. The odds of being born with this condition are 1 in 125 million.

Clinical description

Patients with this disorder are very likely to injure themselves in ways that would normally be prevented by feeling pain. The main features of the disorder are: lack of pain sensation, painless injuries of the arms, legs and oral structures, fever during hot weather because of inability to sweat, mental retardation, infection and scarring of the tongue, lips and gums, chronic infections of bones and joints, bone fractures, multiple scars, osteomyelitis and joint deformities, which may lead to amputation.

Cause

CIPA is caused by a genetic mutation which prevents the formation of nerve cells which are responsible for transmitting signals of pain, heat, and cold to the brain. Overheating kills more than half of all children with CIPA before age 3. The genetic mutation is in the gene encoding the neurotrophic tyrosine kinase receptor (NTRK1 gene).

Treatment

Treatments for CIPA do not always work; however, there are some cases where naloxone may be used as a treatment. Naloxone is a chemical that acts within the nervous system of the body by blocking the nervous system from causing the inactions that occur within the group of cells that receives the message to initiate the sensation of pain, heat, or cold. Most treatments are hard to narrow down for this condition because each CIPA patient may have other conditions including the absence of a sweat gland, nerve fibers, ulcers, and other sub-conditions.

Incidence

CIPA is extremely rare. There are 84 documented living cases in the United States; there are more than 300 in Japan. Only one case is documented in New Zealand, while 2 cases have been documented in Morocco. Only 60 cases had ever been reported until CIPA was first listed as a disorder in 1983. Most of the babies that carry this disease do not live past 3 years of age; and rarely pass age 25. The reason behind the short life span is because when it comes to babies, based upon size and the inability to sweat, overheating kills them easily. Without proper actions, such as monitoring vital signs and temperatures, the parent or guardian will never know if the baby is too hot or cold. The inability to sweat normally leads to recurrent fevers that are unexplained and can be fatal due to hyperthermia. Fevers are normally seen as a time frame of your body's defenses kicking in to fight infections; but if not treated, it can cause febrile fits and death. A high percentage of the individuals who make it past three years suffer from mental retardation and even during their infant years, retardation is more likely because higher body temperature allows more harmful bacteria and virus attacks to occur. In some cases, when infections or viruses attack, blood vessels can swell and cause aneurysms; all of which a CIPA patient will not even feel.

Source : from Wikipedia

Room 706 :
A.A a 2 month old male ,full term ,normal vaginal delivery ,birth weight is 3.5 Kg. , was doing well till age of 1 month when he started to complain from tonic movement of both upper and lower limbs with uprolling of eyes, lasting few seconds 6-7 times/day on daily basis,no Hx of loss of consciousness .
Also there was a Hx of vomiting since birth and it increases in the last 10 days after each meal (Breast milk only).
Since 3 days there was rapid noisy breathing .


Maple syrup urine disease (MSUD), also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia.The condition gets its name from the distinctive sweet odor of affected infants' urine

Diagnosis and symptoms

MSUD is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDH), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products in the blood and urine.

The disease is characterized in an infant by the presence of sweet-smelling urine, with an odor similar to that of maple syrup. Infants with this disease seem healthy at birth but if left untreated suffer severe brain damage, and eventually die.

From early infancy, symptoms of the condition include poor feeding, vomiting, dehydration, lethargy, hypotonia, seizures, ketoacidosis, opisthotonus, pancreatitis, coma and neurological decline.

Classification

Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder may appear later in infancy or childhood and are typically less severe, but still involve mental and physical problems if left untreated.

There are several variations of the disease:

Classic Severe MSUD
Intermediate MSUD
Intermittent MSUD
Thiamine-responsive MSUD
E3-Deficient MSUD with Lactic Acidosis

Management

Keeping MSUD under control requires careful monitoring of blood chemistry and involves both a special diet and frequent testing.

A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage. As these three amino acids are required for proper metabolic function in all people, specialized protein preparations containing substitutes and adjusted levels of the amino acids have been synthesized and tested, allowing MSUD patients to meet normal nutritional requirements without causing harm .

Usually, patients are also monitored by a dietitian. Their diet must be adhered to strictly and permanently. However, with proper management those afflicted are able to live healthy, normal lives and not suffer the severe neurological damage associated with the disease.

Genetic prevalence

Maple syrup urine disease affects approximately 1 out of 180,000 infants. Due in part to the founder effect, however, MSUD has a much higher prevalence in children of Amish and Mennonite descent.

Mutations in the following genes cause maple syrup urine disease:

BCKDHA (Online 'Mendelian Inheritance in Man' (OMIM) 608348)
BCKDHB (Online 'Mendelian Inheritance in Man' (OMIM) 248611)
DBT (Online 'Mendelian Inheritance in Man' (OMIM) 248610)
DLD (Online 'Mendelian Inheritance in Man' (OMIM) 238331)
These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (particularly protein-rich foods such as milk, meat, and eggs). Mutations in any of these genes reduce or eliminate the function of the enzyme complex, preventing the normal breakdown of isoleucine, leucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.

This condition has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Dr. Amira Al-masri
Room 704 :
R.A., a 1 yr. old female known case of MMA admitted via E.R bcz she was in shock, in the E.R they found that the level of ammonia was elevated .
Past Hx. :At the age of 10 months she developed shock and stayed in hospital for 8 days
Family Hx. : 2 died brothers , one at the age of 1 month and the other at 8 months .
Developmental Hx, : she can’t walk till now .