Aurora magazine

X-linked adrenoleukodystrophy, also called X-ALD, is a degenerative genetic disease. People who suffer from it undergo progressive deterioration of the nervous system and endocrine glands. There are three types with different symptoms and age of appearance, all united by the gradual destruction of myelin.

X-ALD is caused by a mutation in the ABCD1 gene, which is found on the X chromosome. The gene codes for the ALDP protein, which is used to eliminate long and very long-chain saturated fatty acids. When the protein levels are too low, the acids build up and damage the glial cells.

The process is still unclear today, but the results are evident: the cells no longer produce myelin, leaving the nerves uncovered. This causes an immune response, resulting in demyelination. The process therefore feeds itself and is impossible to stop, at least with the tools available.

Symptoms vary by variant type and result in three versions of the disease.

• X-linked brain adrenoleukodystrophy (X-CALD), the most common and severe form. It occurs between 3 and 12 years with reduced adrenal activity, learning difficulties, convulsions. The disease leads to the neurovegetative state in the terminal phase.
• Adrenomyeloneuropathy (AMN), form with adult onset. Between 20 and 30 years, limb stiffness, hand pain, weakness occur. Again, it flows into the vegetative state.
• Adrenoleukodystrophy with isolated adrenal cortic insufficiency (AI), affecting 70% of males with X-ALD. In 10% of cases, the only symptom remains. In others, it is the debut sign for the disease.

The diagnosis of the disease takes place starting from clinical observation, followed by an examination of VLCFA levels and magnetic resonance imaging. The genetic test for the ABCD1 gene confirms the diagnosis and also acts as an antenatal diagnosis.

Source: observatoriomalattierare.it

Ornithine transcarbamylase deficiency or OTCD is a genetic disorder affecting the metabolic cycle of the urethra. The deficiency of the enzyme prevents ammonia detoxification, with consequences for the whole organism. In severe cases, it also causes neurological complications.

The disease is estimated to affect around 1 new born out of 56,000, mostly boys. In most cases, the first symptoms occur within days of birth. However, there are also more rare forms of late onset.

The first symptoms are difficulty sucking milk and lethargy, which often turns into a real coma. In some cases, babies exhibit epileptic seizures and hyperventilation. If no immediate action is taken, children can develop an encephalopathy and die in a few days. The milder form occurs instead later, usually at the beginning of weaning.

In adults, the occurrence of ornithine transcarbamylase deficiency is linked to environmental stress. Sometimes it occurs after childbirth or after surgery, or in conjunction with a protein-rich diet. In these cases, the symptoms are nausea, vomiting, delirium. If left untreated, hyperammonaemic coma and neurological complications occur, which can result in cognitive impairment.

If the patient goes into a hyperammonaemic coma, the first thing to do is to reduce the ammonia levels. In the long term, you need to reduce your protein intake and remove nitrogen with special drugs. In severe cases, a liver transplant is needed. Those suffering from the mild form of deficit can live an almost normal life. Unfortunately, the most common and serious form has an almost always poor prognosis.

For diagnosis, the levels of ammonia and other substances in the plasma are analyzed. Later, molecular analyzes are used to confirm the diagnosis. If there have been full-blown cases in the family, prenatal diagnosis can be used.

Source: orpha.net

Chédiak-Higashi syndrome is a rare genetic disorder that affects the immune system. The disease causes a defect in the phagocytic cells, which fail to process and eliminate bacteria. This causes the appearance of giant lysosomal granules in neutrophils, neural cells and others. All this would be caused by an anomaly in the LYST (lysosomal trafficking regulator) gene.

The accumulation of granules causes a wide range of symptoms in patients. The most evident ones are albinism and the tendency to get sick much more often than average, especially due to respiratory infections. In addition, about 80% of patients experience an accelerated phase of the disease. During this time, the patient suffers from fever, jaundice, increased liver and spleen volume, enlarged lymph nodes. Typically, all of this leads to death in about 30 months.

Diagnosis occurs by analyzing a peripheral blood sample, looking for granules. A bone marrow sample is also examined to check the status of the cellular precursors of leukocytes. Genetic tests are used to confirm the diagnosis given by clinical observations. Usually, it is not necessary to examine close relatives, except in suspicious cases.

To date, the only effective therapy is hematopoietic stem cell transplantation. In these cases, approximately 60% of patients survive five years after transplantation. Without a compatible transplant donor, the prognosis is much more negative: most patients die within 7 years of age. Antibiotics can help prevent infections, but they are not a remedial therapy.

Source: msdmanuals.com

Long QT syndrome (LQTS) is a genetic disease that affects the heart. When present, it increases the risk of arrhythmias, syncopes and cardiac arrests. The name derives from the prolongation of the QT interval, a specific electrocardiogram parameter. The disease occurs in the first years of life and, if not diagnosed, can lead to death.

The severity of the disease depends in part on the gene involved and the type of mutation. Depending on the variant, it can occur in children or puberty. Furthermore, it can be transmitted in an autosomal dominant or recessive manner. The first is the most frequent variant and is called Romano-Ward syndrome. The second is rarer and often associated with deafness; it is called Jervell and Lange-Nielsen syndrome. In the latter case, both parents are healthy carriers of the disease.

The most common diagnostic method for LQTS is the resting and stress electrocardiogram. Other basic elements are clinical and family history. At-risk children suffer from frequent syncopations and have had cases of arrhythmia. In addition, there have often been cases of sudden death in the family. After the electrocardiogram and anamnesis, genetic tests are carried out to identify the mutation and the most effective therapy in the specific case.

To date, there is no remedial therapy for long QT syndrome. People suffering from it must take beta-blocker drugs that protect them from arrhythmias. In most cases, enough is enough to prevent symptoms. However, the effectiveness may vary depending on the genetic defect and the severity of the disease. In severe cases, it is necessary to resort to the installation of an automatic defibrillator.

Source: telethon.it