Childhood Cerebral Adrenoleukodystrophy (CCALD)

According to research, PKU is “an autosomal recessive genetic disorder characterized by mental retardation due to a deficiency in phenylalanine hydroxylase, an enzyme necessary to metabolize the essential amino acid phenylalanine to tyrosine. Without phenylalanine hydroxylase, phenylalanine is converted to neurotoxic phenyl pyruvic acid” (Gonzalez, 2009). For those who have PKU, the phenyl pyruvic acid would become quite toxic and lead to damage within the brain causing mental retardation. PKU was first discovered in 1938 by a man named Asbjorn Fölling, and throughout the early 1960s phenyl pyruvic acid was found in urine using a reaction with ferric chloride. However, it was in 1958, that Dr. Guthrie transferred to the Buffalo Children’s Hospital and was able to develop a new approach to measure and monitor

The breakdown of the myelin sheath is caused from a mutation of the gene that makes the Adrenoleukodystrophy protein (ALDP). This ALD protein helps the body metabolize saturated very-long-chain fatty acids found in the serum and tissues of the central nervous system. The newly mutated gene no longer acts as a help aid to breaking down the long-chain fats. Therefore, the body starts accumulating an abnormal amount of fat in the nervous system, adrenal gland and testes that sets off an unusual response in the immune system; demyelination.

Since children lack the HEXA-A gene it causes progressive damage and eventually the nervous system will shut down because it can no longer produce vital neurons needed to function the nervous system and life. Beta-hexosamindinidase is located in the lysosomes, which are structures in cells that act as recycling centers and breaking down the toxic substance. Beta-hexosamidnidase role is toxic and fatty substances called GM2 ganglioside. If the gangliosides become overpowering or too much, can cause destruction of the neurons. The excessive storage of the gangliosides in lysosomes is another factor that causes Tay-Sachs. Tay-Sachs occurs usually when the individual lacks the protein hexosamindinidase A and defected and alterations on chromosome 15 (specifically 15q23-q24). More than 50 mutations having been discovered on chromosome 15 and HEXA-A enzyme. The mutation can vary as in deletion, insertion, and splitting in which each mutation alters the protein. The mutation and disorder cause a decrease in enzymes activity. The severity of the disorder depends on the degree of the enzyme activity and deficiency. For example, one mutation includes, the mutation includes a G-to-T substitution at the 3-inch end of intron 5, which makes a short mRNA. Then skipping exon 6 and the polypeptide lacking 34 amino acids. (Tanaka

Tay-Sachs disease is an autosomal fatal genetic disorder, it is also a form of lipid metabolism disorder. Due to a buildup of fatty substances in

Addison’s disease takes place when the cortex is damaged and does not produce hormones in adequate quantities. Doctors often refer to this condition that involves damage to the adrenal glands as a primary adrenal insufficiency. When the adrenal glands fail to produce adrenocortical hormones it is commonly a result of an autoimmune disease where the body is attacking itself. For an unknown reason the immune system sometimes views the

“Without Hex-A, a fatty substance, or lipid, called GM2 ganglioside accumulates abnormally in cells, especially in the nerve cells of the brain. This ongoing accumulation causes progressive damage to the cells.”http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024672/

common life-shortening disease. More that 1,000 mutations in the CFTR gene have been found in

ADNP Syndrome (Helsmoortel-VanDerAa Syndrome) is a complex neurolodevelopmental disorder in which a defect can affects brain formation, development and function. Any disturbance will affect bran formation, neurodevelopment and will interrupt neuroprotective function and the patient will present with complex disorder that manifest with global developmental delay particularly in motor and speech skills, sleep and behavioural disorder, ASD, hypotonia, feeding difficulties and growth disturbance. Other organ system might be also affected like hearing, vision, immune system, endocrine and cardiovascular system. ADNP is thought to be prevalent among genetic autism cases as it found to be mutated in at least 0.17% of those cases (he…,2014).

CMT can be passed down by sex-linked chromosomes or it can be passed down through autosomal inheritance. Either way, CMT is a mutation of proteins required for the peripheral nervous system. If it’s sex-linked it means the disease is carried on the female sex chromosome X, never on the Y male chromosome. If it’s autosomal it means it’s carried in the DNA, on the genetic chromosomes. It can be recessive, needing two pairs of bad alleles, one from each parent, or it could be dominant only needing one allele from either parent. There are cases where people were affected carrying only one recessive allele, like men for instance (MDA, 2017), where males only have one X, if their X chromosome is a faulty one, it could be missing genetic information it needs to keep rebuilding proteins the body requires for reproduction of those crucial proteins. CMT can pop up and affect anyone at any given time in life, you could live with CMT your whole life and never know you have it, or you could find out you’re a carrier for CMT after you’ve passed it on to your offspring (Al-Thihli, K et al. 2012). As you can tell CMT is passed down through inheritance, we are the cause of the continuing cases for CMT, and we still don’t have a cure to treat the prior cases. It seems the disease is only continuing to be carried in more forms as we diagnose more people and disclose more cases (Vallat, Jean-Michel, 2003).

Alexander Disease is a rare defect involving the nervous system. It is part of a classification of uncommon genetic disorders called leukodystrophies that affect the central nervous system by interfering with the growth and nourishment of the myelin sheath. Myelin sheath shields nerve fibers and promotes rapid transmission of nerve impulses. If myelin is not properly nurtured, the transmission of nerve impulses can become disrupted causing serious impairment of nervous system functions. Although a majority of cases with early onset exhibit a distinct deficiency in the formation of myelin, white matter defects are sometimes not detected in cases accompanying later onset. Contrary to its classification, the universal characteristic among all Alexander disease cases is actually the presence of atypical protein compounds called Rosenthal fibers. They present themselves in a particular type of glial cell found in the central nervous system known as an astrocyte. Glial cells provide nutrients for neurons, absorb dead neurons, and physically reinforce their structure. Rosenthal fibers are composed of substantial quantities of glial fibrillary acidic proteins (GFAP). GFAP is known to sustain the mechanical strength of astrocytes, but in this case it is a defect in GFAP that has been found to interfere with the function of astrocytes and ultimately causes the leukodystrophy. When tested on mice, the mutation of GFAP caused a new, toxic effect, rather

Recently, a new mutational mechanism leading to increase in number of CAG repeated triplets in several human genes responsible for the hereditary disorders was identified [Caskey et al., 1992; Richards et al., 1992]. The cause of disease is expansion of trinucleotide repeat in the androgen receptor (AR) gene on X chromosome at the Xq11^12 (La Spada et al. 1991). The principal pathological manifestation of the SBMA is loss of the motor neurons in spinal cord and the brainstem (Sobue et al. 1989).

Patients with CD are at risk for developing other diseases and disabilities like blindness, mental disabilities and respiratory problems like pneumonia. Those most at risk are individuals with Ashkenazi Jewish decent, with 1 in 40 being a carrier. Since this disease is a recessive genetic disorder, both parents must be carriers for the child to be at risk, so genetic counseling can be an important factor in early diagnosis. There are a few procedures that can be done to prenatally diagnose a child: Chorionic villus sampling and amniocentesis. Although there is currently no cure, symptoms can be managed through pharmaceuticals controlling seizures, muscle stiffness and respiratory issues. Over time, a feeding tube and/or a wheel chair might be necessary to ensure the child’s safety. The average life expectancy for CD patients is 3 to 10 years, yet some individuals can live into their 20s. Researchers are currently studying methods to find a cure or treatment for this progressive disease through gene therapy, which is treating those suffering with the ASPA gene they are deficient in. This is thought to lead to normal breaking apart of the NAA, forming normal myelin and preventing further damage to the white matter in the brain. Studies will continue until they have found a reliable

Batten disease also referred to as Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), is an autosomal recessive neurodegenerative disease, which are genetic diseases that are passed through both parents’ chromosomes. In the United States, approximately three in every one hundred thousand births are diagnosed with batten disease. It is thought to occur mostly in Swedish heritages. Children typically start showing symptoms, at around five to seven years old. The symptoms typically include vision loss, progressive cognitive decline, motor dysfunction, seizures, and behavior problems. The symptoms are shown in both the sexes, but female tend to have the disease more often than male. Females with batten disease commonly have excess of acne, abnormal growth of hair, and androgen, which is a male sex hormone, like testosterone, that are not attributable to medication side effects (Cialone, J. , Adams, H. , Augustine, E. , Marshall, F. , Kwon, J. , et al., 2012). In a study done, females suffering with batten disease have showed more psychiatric problems, especially in the

Researchers are looking into three factors that may cause abnormalities in chemical functioning in the brain and body “genetics, evolution, and infections” (p.36). The biological treatment for such disorders, once the source has been

FTO (fat mass and obesity-associated) also known as alpha-ketoglutarate-dependent dioxygenase is a protein encoded by the FTO gene and is located on chromosome 16. The exact function of this gene is not known. According to the studies, FTO is involved in numerous functions such as DNA repair, nucleic acid demethylation, fatty acid metabolism, and posttranslational modification1. FTO is also important for normal development of the central nervous system and cardiovascular system. Absence of FTO may lead to diseases such as growth retardation, multiple abnormalities and premature death1.