Monday, April 30, 2012

Menkes Disease

Overview

Menkes disease is caused by a defective gene named ATPTA1 that regulates the metabolism of copper in the body. The disease primarily affects male infants. Copper accumulates at abnormally low levels in the liver and brain, but at higher than normal levels in the kidney and intestinal lining. Affected infants may be born prematurely, but appear healthy at birth and develop normally for 6 to 8 weeks.

Symptoms

Floppy muscle tone, seizures, and failure to thrive.  Menkes disease is also characterized by subnormal body temperature and strikingly peculiar hair, which is kinky, colorless or steel-colored, and breaks easily. There is often extensive neurodegeneration in the gray matter of the brain. Arteries in the brain may be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures.

Tests/Diagnosis

Newborn screening for this disorder is not available, and early detection is infrequent because the clinical signs of Menkes disease are subtle in the beginning, the disease is rarely treated early enough to make a significant difference. Recent research sponsored by the NINDS developed a blood test that could be given to newborns at risk for Menkes disease based on a positive family history for the disorder or other indications.

The test measures 4 different chemicals in the blood and, depending upon their levels, can accurately diagnose the presence of Menkes disease before symptoms appear.

Treatments

Study results showed higher survival rates for children given the earliest copper injection treatment and improved, if not normal. However, damage is usually already done since most children are not diagnosed before or right after birth.

Resources
National Institue of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development, The Menkes Foundation

Matthew's Story
I had a normal pregnancy until I was 26 weeks pregnant. At that time, I began going into premature labor frequently. When I was 33 weeks pregnant, I went into labor and had my son, Matthew, on July 31, 2009. He was 4 lbs., 10 oz. and healthy. He was going to be able to leave the hospital with me but he did not know how to suck or swallow and spent two additional weeks in the hospital.

When Matthew came home from the hospital, he did great. Matthew hit all his milestones on time - and even hit some a little early, which is rare for a preemie. Around 10 weeks, he had his first seizure at his babysitter's house. Days later, he got transported to a children's hospital two hours away. He was diagnosed with Dandy-Walker Syndrome with epilepsy and sent home on seizure meds.

We spent the next 3 weeks in and out of the hospital for seizures. We felt like the hospital was not listening to us. We believed there was another problem that was not being addressed. It was almost like Matthew forgot how to do everything he had learned. He had not begun holding his head up before the first seizure and by this point he was about 3 1/2 months old and not even trying to hold it up. We begged our doctor to refer us to Le Bonheur Children's Medical Center in Memphis, TN.

We finally got an appointment with one of their neurologists. Matthew had an EEG but somehow his scheduling got messed up and we had to go back the next day for an MRI. That night, however, we got a call from the neurologist saying he was having seizures almost constantly even when we couldn't tell he was.

After a million tests (or so it felt like) and a little over a week in the hospital, he was unofficially diagnosed with Menkes Disease. A month later, we received the blood test results that were positive.

About 2 months later, we were told he would not live to see his first birthday. He was 6 months old at the time. Now he is almost 3 years old.

Matthew got a G-tube in November 2010 and was put on oxygen in February 2011 but he is still here. He is even in love with his hospice nurse that he has had since Oct. 2010. He is such a joy to all of us. He is our miracle baby.

I made this video about Matthew: http://www.youtube.com/watch?v=sdKklMhwJLY&feature=share

Contributed by MOM Whitney Hamilton - to read more about Matthew check out his Carepage or Facebook

Monday, April 23, 2012

Trichothiodystrophy

Overview
Trichothiodystrophy, which is commonly called TTD, is a rare inherited condition that affects many parts of the body. The hallmark of this condition is brittle hair that is sparse and easily broken. Most affected children have short stature compared to others their age. Intellectual disability and delayed development are common, although most affected individuals are highly social with an outgoing and engaging personality. Some have brain abnormalities that can be seen with imaging tests. Trichothiodystrophy is also associated with recurrent infections, particularly respiratory infections, which can be life-threatening. Other features of trichothiodystrophy can include dry, scaly skin (ichthyosis); abnormalities of the fingernails and toenails; clouding of the lens in both eyes from birth (congenital cataracts); poor coordination; and skeletal abnormalities.

About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) rays from sunlight. They develop a severe sunburn after spending just a few minutes in the sun. Trichothiodystrophy has an estimated incidence of about 1 in 1 million newborns in the United States and Europe. About 100 affected individuals have been reported worldwide.

Symptoms
The signs and symptoms of trichothiodystrophy vary widely. Mild cases may involve only the hair. More severe cases also cause delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.

Tests/Diagnosis
None available.

Treatments
There is currently no treatment with TTD.

Resources
http://ghr.nlm.nih.gov/condition/trichothiodystrophy


Contributed by MOM Ashley Cunningham

Monday, April 16, 2012

Barth Syndrome (BTHS)

Overview: Barth syndrome (BTHS) is a rare, sex-linked genetic disorder of lipid metabolism that primarily affects males across different ethnicities. Typically, boys with BTHS present with hypotonia (low muscle tone) and dilated cardiomyopathy (labored breathing, poor appetite, and/or slow weight gain) at or within the first few months after birth. Other important features of BTHS include bacterial infections because of neutropenia (a reduction in the number of white blood cells called neutrophils), muscle weakness, fatigue, and growth delay. Although most children with BTHS manifest all of these characteristics, some have only one or two of these abnormalities and, as a result, often are given incorrect diagnoses.

Barth syndrome occurs in many different ethnic groups and does not appear to be more common in any one group. To date, there are no good studies of the population or birth incidence of BTHS. The gene for Barth syndrome, tafazzin (TAZ, also called G4.5), is located on the long arm of the X chromosome (Xq28). Mutations in the tafazzin gene lead to decreased production of an enzyme required for the synthesis of “cardiolipin,” a special lipid that is important in energy metabolism.
 
Symptoms:

Cardiomyopathy
A weak heart muscle usually associated with enlargement of the heart (usually dilated with variable myocardial hypertrophy, sometimes with left ventricular noncompaction and/or endocardial fibroelastosis).

Neutropenia
(Chronic, Cyclic, or Intermittent) A reduction in “neutrophils,” a type of white blood cell that is most important for fighting bacterial infections. Neutropenia may predispose an individual to mouth ulcers, fevers and bacterial infections such as bacterial pneumonia and skin abscesses.
Underdeveloped Skeletal Musculature and Muscle Weakness All muscles, including the heart, have a cellular deficiency which limits their ability to produce energy. Muscle weakness and increased exertional fatigue are characteristic findings in BTHS.

Growth Delay
During childhood most affected individuals are below-average in height and weight. This is often assumed to be evidence of poor nutrition or other secondary effects of a chronic illness, but that is rarely the case. In fact, some of the common nutritional treatments are contra-indicated. Through BSF´s registry, we have observed a growth pattern similar to but often more severe than constitutional growth delay with accelerated growth to normal height during mid- to late- teenage years.
Exercise Intolerance
Cardiolipin Abnormalities
A failure of BTHS mitochondria to make adequate amounts of tetralinoleoyl-cardiolipin, an essential lipid (fat-like molecule) for normal mitochondrial structure and energy.


3-Methylglutaconic Aciduria, Type II (MGA, Type II)(Typically a 5- to 20-fold increase in an organic acid that can be measured in urine) A result of abnormal mitochondria (the “powerhouses” or primary energy producers in cells) function. However, there have been reports of normal levels of 3-methylglutaconic acid (3MGA) in confirmed cases of BTHS.
Testing/Diagnosis: 

Like many genetic disorders, Barth syndrome is quite variable among different families and sometimes even within a single sibship. Whereas at least 80% of known patients with Barth syndrome manifest all four principal diagnostic criteria at some time during childhood, any or possibly even all of the cardinal findings may be absent in a boy with a proven mutation in the Barth gene. This variability in presentation of symptoms and severity in phenotype makes Barth syndrome a difficult disorder to diagnose. In absence of a family history of related illnesses, the clinician is presented with the challenge to diagnose a child who inherits the disorder through a spontaneous mutation. The diagnosis of Barth syndrome should be considered for any child or adult found to have any one of its four cardinal clinical characteristics, and evaluation for the other diagnostic criteria should be undertaken by obtaining the following studies:
  1. Quantitative urine organic acid analysis including quantification of 3-methylglutaconic acid (Type II)
  2. Complete blood count and differential
  3. Echocardiogram
  4. Analysis of growth parameters from birth

Treatments:
There is no specific treatment for BTHS, but each of the individual problems can be successfully controlled, and short stature often resolves after puberty.

Resources/Support and info at BSF:
University of Mississippi Medical Center


Christopher's Story
Christopher was born with a congenital heart defect known as cardiomyopathy. At 22 months this was found to be caused by a rare X linked form of mitochondrial disease called Barth syndrome. His chances of survival were not good, and he was placed on hospice care. Much to his doctors amazement his cardiomyopathy improved. He still has many struggles including severe cyclic neutropenia and muscle weakness. He is a: living, breathing, daily reminder that miracles happen. His parents cherish every moment they have with him. His mother works hard to spread awareness about a disease she believes is severly underdiagnosed.

Contributed by MOM Kristi Pena- For more about Christoper, check out his Carepage

Monday, April 9, 2012

Rare Dysmotility Syndrome (RDS)

Overview: Rare Dysmotility Syndrome is a rare gastric disorder (having to do with the gastrointestinal track).  This disorder causes the motility of the stomach and intestines to be extremely slow which often leading to not being able tolarate food.  It also causes slow gastric emptying -  taking a long time to be digested.  It's not certain if the cause is prematurity or genetic.  There is also belief that ascites may be related to this condition.  There are not many cases of RDS registered in the US.
Symptoms:
  • Some of the known symptoms with RDS include:
  • slow digestion
  • weight loss
  • failure to thrive
  • swallowing problems and poor oral motor skills
  • distended abdomen
  • excessive gas or inability to pass gas
  • reflux or GERD
  • anorexia
  • chronic constipation or diarrhea
  • vomiting
  • unable to tolerate feeding without distention.
  • laboratory chemistries, unbalanced electrolytes
Testing/Diagnosis:  To diagnose RDS a doctor may order an upper or lower GI (an image study to observe the body and how it digests food.  Genetic testing as well as testing for Cystic Fibrosis is often order.  In some cases doctors may also request a biopsy of the intestines.  The best test to document delayed gastric emptying is a nuclear scintigraphy test (gastric emptying study). In this test a radiolabeled meal is ingested and the radioisotope is followed so that a time curve can be plotted to determine how long it takes for the stomach to empty. This is compared to a "normal" curve. Generally, a t1/2 (time it takes to empty half the meal) of greater than 90 minutes is considered abnormal.

Treatments: 
Some medications may help with RDS, such as different types of anti bacterials to help kill the bacteria along the intestinal wall.  Feeding tubes (often J tubes in order to bypass the stomach completely) can help with the feed intolerance.  Often doctors will suggest/prescribe elemental formula's.  An elemental formula is one that is already broken down as it would be during normal digestion.  There are many different types of elemental formulas, some are more broken down than others. There are medications that can be used for treating these diseases, for example metoclopramide or cisapride, but these usually are of benefit in the milder cases. Because of the rarity of these diseases the management of patients usually is turned over to "sub - subspecialists," gastroenterologists with special expertise in disorders of motility.

Resources:
http://www.nationwidechildrens.org/motility-center
http://www.pedsgi.org/
https://www.facebook.com/pages/PEDS-Pediatric-Digestion-and-Motility-Disorders-Society-Inc
http://www.inspire.com

Aizen's Story
 
We went through so much trying to figure out why our preemie, Aizen,  wouldn't eat.  We could not figure out why his tummy was so distented.  He was put through so many tests and lab work, all coming back negative.  The doctors finally diagnosed Dysmotility Syndrome. Even though they are not completely sure about the diagnosis, they are treating Aizen for this syndrome.  So far treatment has been successful.

Contributed by MOM Ashley Lembert

Monday, April 2, 2012

Fumaric aciduria (FA)

Overview: Fumarase deficiency (also known as Fumaric aciduria or FA) is extremely rare, with only thirteen diagnosed and identified cases worldwide until roughly 1990. (FA is an exceptionally rare condition characterized by a deficiency of the enzyme fumarate hydratase, leading to vast elevations of fumaric acid in the urine. Fumaric acid, or fumarate, is a metabolite in a cellular energy production pathway known as the Citric Acid Cycle or Kreb’s Cycle. In individuals with FA fumarate hydratase is deficient, disallowing fumarate to be converted into malate, the next step of the Kreb’s Cycle. Thus the pathophysiology of FA is intimately linked to cellular energy metabolism.

Characteristics/Symptoms
: Fumarase deficiency causes encephalopathy, severe mental retardation, unusual facial features, brain malformation, and epileptic seizures due to an abnormally low amount of fumarase in cells. It can initially present with polyhydraminos on prenatal ultrasound. Affected neonates may demonstrate nonspecific signs of poor feeding and hypotonia. Laboratory findings in neonates may indicate polycythemia, leukopenia, or neutropenia. As they age, neurological deficits begin to manifest with seizures, dystonias, and severe developmental delay.
The list of signs and symptoms mentioned in various sources for Fumaric aciduria includes the 10 most common listed below:

Tests/Diagnosis: blood and urine laboratory chemistries, bladder, kidney and urinary imaging and laboratory values, and MRI

Treatment Options: Currently no known treatments other than management of symptoms, seizure control, various gross and fine motor therapies, possible pharmocological options for management of aciduria or lactic acid imbalances.  If mitochondrial in origin, mitochondrial protocols should be closely followed for emergency situations.

Support/Information:
http://www.experienceproject.com/groups/Have-Fumaric-Aciduria/95269



Luc's Story:
Right now hes not having any its truly a blessing he is a bright happy, healthy , baby hes a little behind with milestones but over all not doing to bad he has bad refux and digestion problems with is still a struggle but under control !!  He has seizures but nothing that is not controllable with what he's been hit with.  Overall is he doing well, but he is only 8 months old.  I hope he grows up to be a normal, healthy, happy baby child. We currently do not have any treatment options other than some homeopathic remedies such as organics, fish oil, homemade milk, osteopathy and massage, and many therapies.  Support is difficult to find, though some online support is available. I struggle with not knowing much about what we are facing or what we should be doing.