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They are a set of diseases characterized by the accumulation and persistence of toxic substances as a result of an absence or defect in one or more enzymes. It is important in all cases to make an early diagnosis thanks to the clinical suspicion of experts due to the presence of specific symptoms and signs, which leads to a rapid establishment of adequate treatment. Early intervention by multidisciplinary groups prevents long-term sequelae in patients.

Target: Babies

What is it?

Deficiencies in the synthesis of primary bile acids are disorders in sterol metabolism secondary to deficiencies in one of the enzymes that participate in these processes, leading to the presentation of cholestasis, malabsorption, and can progress to cirrhosis, with subsequent insufficiency. hepatocellular and liver failure. They are diseases of autosomal recessive inheritance and given their very low prevalence they are considered ultra-orphan diseases. (1)

What types of deficiencies are there?

There are seven hereditary defects that cause hepatic cholestasis, among which the most frequent in their presentation are 3beta-hydroxy-D5-C27-steroid dehydrogenase/isomerase (3b-HSD) deficiency and Delta4–3-oxsteroid deficiency -5beta-reductase (D4–3-oxoR), which interfere in the initial phases of bile acid synthesis by modifying the steroid nucleus of cholesterol. (1.2)

When to suspect?

This type of deficiency should be suspected with some signs that are nonspecific but can guide the diagnosis, such as: cholestasis and/or hepatocellular insufficiency from the first years of life, with subsequent jaundice (yellow discoloration of the mucous membranes) with the absence of pruritus, malabsorption syndrome, normal GGT test, among other parameters; however, it should be noted that the confirmatory test for these diseases to make the definitive diagnosis is performed through the analysis of serum and urine bile acids with gas chromatography with mass spectrometry (GC-MS) for the analysis of toxic metabolites . (1.2)


  • Setchell KDR and Heubi JE. Defects in Bile Acid Biosynthesis, Diagnostic and Treatment. J Pediatr Gastroenterol Nutr,2006; Vol. 43 (1) 17- 22.
  • Jahnel J, Zöhrer E, Fischler B, D’Antiga L, Debray D, Dezsofi A, et al. Attempt to Determine the Prevalence of Two Inborn Errors of Primary Bile Acid Synthesis: Results of a European Survey. JPGN 2017;64 (6): 864–868.

Target: It may present itself at any age

What is it?

Homozygous familial hypercholesterolemia (HoFH) is a rare hereditary disease, characterized by an excess of surrounding LDL lipids in the blood (up to six times more than normal). Given its accumulation in the walls of the vessels, various implications are presented at the cardiovascular level which can be life-threatening. These patients suffer from atherosclerotic disease from very early ages, which leads to the presentation of acute myocardial infarction (AMI), cerebrovascular accident (CVA) or sudden death. (1.2)

Which are the symptoms?

Taking into account the high levels of circulating lipids in the blood, these usually appear as deposits in different parts of the body, being evident, for example, in the skin and tendons called cutaneous xanthomas, around the eyelid called xanthelasmas, or deposits in the cornea known as arcus corneal. (1.2)

What to take into account?

Given the cardiovascular implications described, patients benefit from an early and timely diagnosis in order to initiate changes in lifestyle (adjustment in diet and physical activity) accompanied by pharmacological management that lowers blood lipid levels, as deemed appropriate. the treating physician. It should be noted that the diagnosis is clinical, based on the patient’s signs and symptoms, as well as the history and family history. (1.2)


  • Merchán A, Ruiz AJ, Campo R, Prada CE, Toro JM, Sánchez R, et al. Hipercolesterolemia familiar: artículo de revisón. Rev Colomb Cardiol. 2016;23(4):4–26.
  • Ascaso JF, Mata P, Arbona C, Civiera F, Valdivielso P y Masana L. Hipercolesterolemia familiar homocigota: adaptación a España del documento de posición del grupo de consenso sobre hipercolesterolemia familiar de la Sociedad Europea de Arteriosclerosis. Documento de Consenso de la Sociedad Española de Arteriosclerosis (SEA) y la Fundación Hipercolesterolemia Familiar (FHF). Clin Invest Arterioscl. 2015;27(2):80—96.

Target: Babies

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 [1].

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 [1]. 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 [2].

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 [2].

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 [4]. 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,
  • Human Molecular Genetics, Volume 28, Issue R1, October 2019, Pages R42–R48,
  • 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.

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.