Aurora magazine

Hereditary hemochromatosis is a genetic disease that causes an accumulation of iron in the body. The classic form is the most common and appears in adulthood, often remaining asymptomatic throughout life. The most obvious consequences usually occur with the passing of the years: chronic fatigue, joint pains, cirrhosis of the liver, heart problems, diabetes.

There is also a juvenile form, more severe and that occurs between 10 and 20 years with serious heart problems. The third form is intermediate between the first two, while the fourth is the most heterogeneous. In some cases it resembles the classical form, while in others it is more benign.

The first three forms are all caused by the malfunction of hepcidin, the iron hormone. The fourth is instead focused on ferroportin, the target of the action of the first hormone. The hormonal anomalies in question are related to the alterations of different genes, with also different modes of transmission.

Classical form, HFE gene and autosomal recessive mode.
Juvenile form, HAMP and HJV genes with autosomal recessive modality.
Third form, TFR2 gene and autosomal recessive mode.
Fourth form, mutations in the gene coding for the ferroportin protein and autosomal dominant mode.

The first signs of hereditary hemochromatosis are the altered values ​​of iron in the blood. At this point we continue with an analysis of liver deposits in the liver, which are increased. To do this we use an MRI or a liver biopsy, in rarer cases. The final confirmation comes from genetic analysis.

The standard therapy includes the salassotherapy, or the withdrawal of about 400 ml of blood per week. It is done 2-6 a year depending on the needs, as long as the iron values ​​have not returned to normal. Those who can not do the salts use chelators, drugs that capture iron. If action is taken before the iron damages the liver, life expectancy is normal.

Source: telethon.it

Lamellar ichthyosis is a genetic disease that manifests itself at birth. The baby's skin is wrapped in a transparent membrane, which breaks and falls within 10-14 days. Before this time, the membrane hinders breathing and causes abnormalities in the eyelids and lips. Its fall, on the other hand, causes loss of fluids, risk of infections, difficulty in regulating body temperature. Later, the skin thickens and forms scales.

The scales are concentrated mainly at the joints. In some cases, hair and nail changes also occur. Beyond the psychological and physical discomfort caused by the symptoms, however, there are no real physical dangers for those who suffer from it. The subjects do not have available treatment cures, but can resort to symptomatic treatments. Retinoids and emollients soften the skin, while the keratolytic ones remove the scales.

Lamellar ichthyosis is caused by a mutation of the TGM1 gene and is transmitted in an autosomal recessive manner. In order for it to occur, both parents must be healthy carriers and transmit the anomaly to the child. However, cases of ichthyosis with autosomal dominant transmission have been reported, in which a sick parent has transmitted the disease. In the latter case, there is a 50% chance that a child will show the disease.

Lamellar ichthyosis is diagnosed by observation of symptoms, also evident at the time of delivery. Afterwards, doctors perform a skin biopsy to confirm the diagnosis.

Source: telethon.it

Noonan syndrome is a genetic disease with an incidence of 1 case per 1000-2500 newborns. It includes a wide variety of clinical manifestations, but the most common are congenital heart disease. In addition to these, which affect almost 70% of patients, other symptoms are:

• short;
• lowering of the eyelids;
• spaced eyes;
• big ears;
• chest malformation;
• cognitive deficits;
• lack of descent of the testes in the scrotum.

Diagnosis takes place starting from the observation of the above symptoms. An analysis of family history follows, with the confirmation of a genetic investigation. Although some of the genes involved are known, in some cases the genetic cause remains unknown. Furthermore, the clinical variability of the disease makes the diagnosis much more difficult. Nevertheless, if there are family cases, prenatal diagnosis can be used.

Noolan syndrome is a hereditary and sporadic genetic disease. In the first case, transmission occurs in an autosomal dominant manner: to develop the disease, a copy of the altered gene is sufficient. In 50% of cases, the affected gene is PTPN11; in all other cases, mutations affect the KRAS, NRAS, RAF1, BRAF and SOS1 genes. However, only 75% of patients show identifiable and clear genetic variants.

For the moment there is no resolution therapy for Noolan syndrome. Several studies are underway on drugs that could inhibit the activity of mutated enzymes. Cardiac lesions are treatable with surgery and in some cases hormone therapy is recommended. If followed appropriately, children can reach adulthood without problems.

Source: telethon.it

Canavan's disease is a genetic neurodegenerative disease, prevalent among Ashkenazi Jews. This term defines the descendants of the Jewish communities that settled in the Reno valley during the Middle Ages. Among the latter, the incidence is 1 case for every 6,400-13,500 newborns, if both parents are Ashkenazi Jews. In the rest of the population, however, the incidence is 1 case for every 100,000 newborns.

The pathology has two forms.

• mild form, which only causes a slight delay in development and occurs during childhood. It is the rarest form.
• Severe form, which causes leukodystrophy, macrocephaly and a marked delay in development. It is the most widespread form of the disease and manifests itself in the neonatal period or in childhood.

Children suffering from severe form present neurological damage and high concentrations of N-acetyl-L-aspartic acid (NAA). High levels of acid can be found in urine, blood and cephaloracidian fluid. All this leads to a serious delay in development. In contrast, in the mild form the levels of the substance are much lower and the delay is also lower.

Canavan disease is linked to mutations in the ASPA gene, which encodes the enzyme aspartoacylase. The mutations are many and can cause both the decrease and the cancellation of the enzymatic activity. Many Ashkenazi Jews have two genetic mutations in particular. Furthermore, those with mild form tend to have a mild and severe mutation.

The prognosis varies depending on the form of the disease. Children who suffer from severe form have an average survival of about 10 years. Those who suffer from the mild form, on the other hand, have an expectation of normal life.

Source: orpha.net