Aurora magazine

Costello syndrome is a disease that affects around 300 people worldwide. It is caused by mutations in the genes that control the development and division of cells from different organs. In about 80% of patients, the anomaly causes changes in the amino acids p.Gly12Ser. Unfortunately, this causes variable symptoms, which makes diagnosis difficult. The only reliable criterion is genetic analysis.

Children with Costello syndrome are born underweight and struggle to feed themselves, so much that forced feeding is necessary. The chicks grow more slowly than the average and are of short stature, often afflicted by a moderate mental disability. In some cases, the disease also causes macrocephaly, muscle and skeletal malformations, cardiovascular problems. Delays in growth also cause puberty to shift forward, which is contrasted by the symptoms of premature aging in adulthood.

Costello's syndrome is in many ways similar to other diseases, which hinders its correct diagnosis. People with family cases can resort to prenatal diagnosis. In order for the tests to be effective, however, it is necessary to know the genetic mutation that runs in the family.

The treatments available today focus on the symptoms of the disease. Doctors therefore act on any cardiovascular problems, even with surgery. Specific intellectual strategies are used for intellectual problems. Periodic checks are used to counteract the development of tumors - a very present event in this disease.

Source: orpha.net

A team of South African researchers has identified the genetic variant that causes a very rare disease. It is a neurodegenerative condition that occurs between 12 and 14 months, causing loss of muscle tone and epileptic seizures. To date, only three children in the world suffer from this particular disease and two live in South Africa.

Doctor Alicia Byrne started with the analysis of a single patient. The child presented a series of symptoms common to different diseases, the combination of which however was impossible to link to a single cause.

The scientific literature did not describe any pathology superimposable 100% with that from which the child suffered. The doctor then started looking for similar cases and found two more. Once the three children with the same symptoms were identified, the researchers sequenced their DNA. Thanks to sequencing, anomalies emerged that hinder the absorption of the B vitamins.

The vitamins in question are essential for the development and proper functioning of the nervous system. When they are missing, the problems identified in the three children occur. The discovery allowed the development of a treatment capable of slowing down the disease. Thanks to weekly injections of vitamin B, doctors have reversed part of the devastating symptoms of the disease. The next step will be to develop prenatal and neonatal genetic tests in order to diagnose the disease before it starts damaging the nervous system.

Source: unisa.edu.au

Benign familial familial myoclonic epilepsy is an inherited form of epilepsy. Unlike other forms, it causes neither early dementia nor cerebellar ataxia. However, it manifests itself with cortical tremors in the hands and occasional seizures.

The first symptoms appear between 11 and 50 years of life; in most cases, it occurs for 20 years. At the beginning there is a short tremor in the hands, characterized by contractions that worsen in stressful conditions. As the person ages, the tremors become more severe. In rare cases, tonic-clonic seizures also occur, concentrated mainly around the age of 30. Again, stress exacerbates the symptoms. Familial myoclonic epilepsy is autosomal dominant.

The researchers identified four possible chromosomal loci that could be related to its appearance. The different loci appear to be linked to the patient's ethnic group and would also influence the symptoms. For now, the diagnosis is mainly based on clinical and electrophysiological analyzes: the electroencephalogram is used to identify anomalies in the traces.

Despite efforts, providing an accurate diagnosis is often difficult. Most sick people receive the wrong diagnosis of progressive myoclonic epilepsy, which instead leads to dementia and ataxia. Genetic counseling is possible if a family member has already received a diagnosis. To date there is no definitive treatment: beta-blockers are not very effective, while antiepileptics give some benefit. On the other hand, life expectancy remains unchanged.

Source: orpha.net

Nonaka distal myopathy - also called GNE myopathy - is a rare genetic disorder widespread especially in Japan. Causes progressive loss of muscle strength and manifests itself around the age of 30. For the moment there are no definitive treatments.

The first symptom consists in weakness in the hands and feet, which spreads to the calves and arms. As the disease progresses, it also affects the rest of the legs and shoulders. The cardiac, pharyngeal and ocular muscles that continue to function are usually spared. Respiratory muscles are involved only in the later stages of the disease.

The disease is caused by an anomaly in the GNE gene, which codes for the enzyme responsible for the production of sialic acid. The mutation causes a decrease in enzyme levels by 30% -60%. The result is a reduction of the sialylation of glycoproteins and glycolipids, with consequent reduction of proteins. The muscles therefore remain without the bricks needed to develop and function properly.

The diagnosis of Nonaka distal myopathy starts from the observation of the "falling foot". Then the doctors check for a possible history in the family, which could give rise to a genetic predisposition. In this case, we proceed with a muscle biopsy, which serves to identify changes in the muscle fibers. In fact, the absence of proteins causes entire empty areas. Genetic testing is usually used to confirm the diagnosis.

The disease forces patients on a wheelchair within 15 to 20 years. To date there are no effective therapies and symptoms can only be treated. Sialic acid supplements can help and some genetic therapies are being studied.

Source: orpha.net