Target: children (men)
What is it?
Duchenne muscular dystrophy (DMD) is a neuromuscular pathology of inheritance linked to the X chromosome, caused by a defect in the gene that codes for the production of the protein dystrophin, essential for proper muscle function1. Due to its inheritance pattern, DMD mainly affects males, with an incidence of 1/3,500-6,000 male births [2, 3].
¿Cuáles son sus síntomas?
The first symptoms and signs of DMD appear around 3 to 5 years of age. Patients with DMD present progressive muscular deterioration, generating difficulty in the ability to walk (ambulation), muscle cramps, fatigue, and pulmonary and cardiac failure, ultimately resulting in reduced life expectancy [1, 5, 6, 7 , 8].
The absence of treatment translates into a loss of early ambulation, between 11 and 12 years of age1-3 which leads to the need for adaptive equipment or assistance to be able to carry out basic activities of daily living .
Historically, the life expectancy of patients with DMD is 20 years, given the complications that can occur on the lung and heart muscles, which translates into fatal outcomes .
How is it diagnosed?
To diagnose DMD, the patient’s symptoms and signs must be correlated with the results of the following studies :
Measurement of serum levels of muscle enzymes (creatine phosphokinase)
Genetic analyzes such as MLPA (multiple ligand dependent probe amplification) or chromosome microarray
Muscle biopsy, in cases where genetic analyzes are inconclusive
It is essential that the diagnostic approach is always carried out by specialist medical professionals.
Which are the treatments?
To carry out an adequate treatment of DMD, a multidisciplinary group is required in order to maintain the patient’s quality of life, provide symptomatic support and treat possible complications [1, 2].
Advances in the treatment of DMD have been significant and have resulted in marked improvement in survival and quality of life for patients [1-4]. Standard therapy for DMD includes treatment with corticosteroids to manage the complications of the disease, but it does not resolve the genetic defect.
In recent years, novel therapies have emerged whose objective is to offer a specific treatment for the genetic mutation, known as antisense therapy, based on the use of complementary oligonucleotides to a specific sequence of the gene, which allow the mutation to be omitted and thus increase dystrophin e positively impact ambulation and lung function, being for these patients an alternative for modifying the natural outcome of the disease [1,5].
- Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health. 2015 Aug;51(8):759-64.
- Ortez C, Natera de Benito D, Carrera García L, Expósito J, Nolasco G, Nascimento A. [Advances in the treatment of Duchenne muscular dystrophy]. Medicina (B Aires). 2019;79 Suppl 3:77-81. Review. Spanish.
- Orpha.net. Portal de información de enfermedades raras y medicamentos huérfanos. (05 noviembre de 2019). Distrofia muscular de Duchenne. Disponible en: https://www.orpha.net/consor/www/cgi-bin/OC_Exp.php?lng=ES&Expert=98896
- Eagle M, Bourke J, Bullock R et al. Managing Duchenne muscular dystrophy – the additive effect of spinal surgery and home nocturnal ventilation in improving survival. Neuromuscul. Disord. 2007; 17: 470–475.
- Kole R, Kramer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonudeotides Nat Rev Drug Discov. 2012;11(2):125-140. doi:10.1038/nrd3625
- Bimkrant DJ. Bushby K. Bann CM. et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation. endocrine. And gastrointestinal and nutritional management Lancet Neurol. 2018;17(3):251-267
- Emery A. Muntom F. Quinilivan R Duchenne Muscular Dystrophy. 4th ed. Oxford. England: Oxford University Press; 2015
Aartsma-Rus A.van Deutekom JCT. Fokkema IF. van Ommen G-JB. Den Dunnen JT. Entries m the Leiden Duchenne muscular dystrophy mutation database: an Overview of mutation types and paradoxical cases that confirm the reading-frame rule Muscle Nerve. 2006:34(2); 135-144.
Target: Most cases occur between the ages of 5 and 35. 3% can present beyond the fourth decade
What is it?
Wilson’s disease is a hereditary disorder characterized by a deficient biliary excretion of copper, producing its accumulation in the liver, brain (basal nuclei) and corneal, mainly. What causes a multiple clinical presentation.
It is caused by mutations in the ATP7B gene on chromosome 13, which encodes a type B copper transporter located in the trans Golgi network of hepatocytes, through autosomal recessive inheritance.
Wilson’s disease is not just a disease of children or young adults, it can occur at any age. The prevalence of the disease is 1 per 30,000 individuals. Most cases occur between the ages of 5 and 35. 3% can present beyond the fourth decade.
Its presentation can vary greatly from patient to patient, presenting from neurological and hepatic symptoms, to psychiatric, but a large proportion present a clinical sign called: Kayser Fleischer’s sign, which, although not pathognomonic, does help suspect Wilson’s disease .
How is the diagnosis made?
Its diagnosis requires the sum of various signs and symptoms, and paraclinical findings, which would yield a sufficient score to rule out or confirm the disease, known as the Lipzing scoring system.
What is the treatment?
Wilson’s disease includes the use of a chelator, where the use of trientine is indicated for the treatment of the disease, also taking into account that according to the EASL Clinical Practice Guidelines, trientine would be better tolerated than other medications that could also be use.
What is it?
They are hereditary metabolic diseases (recessive or linked to the X chromosome) that are derived from an anomaly, qualitative or quantitative, of one of the six enzymes that participate in the synthesis of urea. Causing a crisis of hyperammonemia that puts the patient’s life at risk .
Why does hyperammonemia occur?
Nitrogen is a waste product that comes from protein intake and must be excreted from the body as urea present in the urine. The inadequate excretion of nitrogen causes an accumulation of ammonia, in toxic levels for the organism called: hyperammonemia, which puts life at risk . Survivors of metabolic decompensation frequently suffer from severe neurological sequelae related to the accumulation of ammonia in the brain. Early diagnosis is definitive for the patient’s prognosis, since pharmacological therapy allows maintaining normal ammonium levels .
Which are the symptoms?
In severe enzyme defects, symptoms appear in the first 24 to 48 hours of life. Post-infant newborns present with drowsiness, changes in temperature, decreased intake followed by vomiting, lethargy, and coma. Therefore, it can be easily confused with sepsis, however, when no signs of infection are found, a metabolic disorder should be suspected and ruled out. Approximately 50% of newborns with hyperammonemia have seizures .
To take into account
The presentation of neonatal-onset disease is the most frequent due to severe enzyme deficiency, accounting for 60% of cases; the most frequent deficiency: ornithine transcarbamylase (OTC). Sodium Phenylbutyrate is indicated for the long-term treatment of urea cycle disorders with carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinate synthetase (ASS) deficiency. This therapeutic formula is a multilayer granulated solution that masks the taste of the active ingredient, which does not require special storage. The evidence shows that in the follow-up of up to 11 months in pediatric patients, no episodes of metabolic decompensation were observed with the use of sodium phenylbutyrate. This comes with a calibrated dispenser adapted for pediatric use to ensure proper dosage and adherence . Therefore, this treatment is effective and improves the quality of life of patients with TCU.
- Carretero, M.C. Fenilbutirato de Sodio. Offarm. Elseiver. Vol 23. Num. 10 pag 132 134. Nov. 2004.
- Leandro R Soria, Nicholas Ah Mew, Nicola Brunetti-Pierri, Progress and challenges in development of new therapies for urea cycle disorders, Human Molecular Genetics, Volume 28, Issue R1, October 2019, Pages R42–R48, https://doi.org/10.1093/hmg/ddz140
- Human Molecular Genetics, Volume 28, Issue R1, October 2019, Pages R42–R48, https://doi.org/10.1093/hmg/ddz140
- Kibleur Y, Dobbelaere D, Barth M, et al. Resuls from a Nationwide Cohort Temporary Utilization Authorization (ATU) Survey of Patients in France Treated with Pheburane (Sodium Phenylbutyrate) Taste-Masked Granules. Pediatric Drugs 2014; 16(5): 407-415.