メバロン酸

/SIGNS AND SYMPTOMS/ Defects of cholesterol biosynthesis comprise a heterogeneous group of disorders... . Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS) are due to allelic defects in mevalonate kinase, an enzyme located proximally in the pathway of cholesterol and nonsterol isoprene biosynthesis. Clinically, patients affected with these disorders present with recurrent febrile attacks. This is the only manifestation in most patients with HIDS, and, in the case of classical mevalonic aciduria, is part of a severe multisystemic disease, including malformations, severe failure to thrive and neurological abnormalities. ... The diagnosis of MVA and HIDS is based on determination of mevalonic acid in urine followed by determination of enzyme activity...

/SIGNS AND SYMPTOMS/ The febrile crises /in mevalonate kinase deficiency/ are similar to those observed in hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Pathogenic mutations in the mevalonate kinase gene in both disorders have demonstrated a common genetic basis.

/CASE REPORTS/ Mevalonic aciduria is a rare disease that is a consequence of a deficiency of mevalonate kinase, an inborn error in the biosynthesis of cholesterol. Approximately 30 cases have been reported. ... Data on two siblings with mevalonic aciduria /are contributed/ to the recognition of this subject. Both were born after uneventful pregnancies. Their parents were healthy and not consanguineous. They had normal somatic and psychomotor development until they were around 2 years old. After the second year of life they developed mental retardation, ataxia and hypotonia. MRI showed cerebellar atrophy of both hemispheres and vermis. One sibling, from the age of 10 years onwards, suffered from complex partial seizures that were controlled with levetiracetam and lamotrigine. At 11 and 12 years of age, respectively, they were able to walk without help, but their gait was broad and ataxic. Their speech was dysarthric, fine motor skills were impaired as result of cerebellar ataxia, and they had moderate mental retardation. Diagnosis of mevalonic aciduria was made at this age through urinary organic acid analysis by gas chromatography-mass spectroscopy, which revealed high urinary excretion of mevalonic acid. They are currently 18 and 17 years old, respectively, show mental retardation and are able to walk but with difficulty. In our patients, ataxia due to cerebellar atrophy and mental retardation have been the predominant clinical manifestations. In mildly affected patients who survive infancy, these seem to be the predominant findings.

/CASE REPORTS/ The analysis of amniotic fluids of two pregnancies at risk for mevalonic aciduria showed a 3277-fold elevation as compared to controls in the first case, diagnostic of an affected fetus, and a normal value in the second one. Mevalonic acid concentration was much increased in tissues of the affected and aborted fetus. Concentrations ranged from 840 to 1120 mumol/kg in various tissues and were as high as 1810 umol/kg in brain. Concentrations in control fetal tissues were approximately 1 umol/kg.

For more Human Toxicity Excerpts (Complete) data for MEVALONIC ACID (7 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/