Informace o publikaci
Aminoacylase 1 deficiency: the first Czech patient
| Název česky | První český pacient s deficitem aminoacylazy 1 |
|---|---|
| Autoři | |
| Rok publikování | 2023 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Introduction: Aminoacylase 1 (ACY1D) deficiency (MIM 609924) belongs to rare inherited metabolic disorders and is characterized by increased urinary excretion of N-acetylated amino acids (serine, glutamic acid, alanine, methionine, glycine, leucine and valine). The disorder is inherited in an autosomal recessive manner, the ACY1 gene (104620.0001) is located in the 3p21.2 region. The disease was first described in 2005 by Van Coster. So far, about 20 patients have been detected in the world. The enzyme aminoacylase 1 (EC 3.5.1.14) catalyzes the deacetylation of N-acetylated amino acids into L-amino acids and an acetylated group. The disease is most often manifested by neurological and psychiatric impairment, psychomotor retardation, muscle tone disorder, more often muscle hypotonia and weakness, convulsions, retardation of the expressive component of speech, growth retardation, sensorineural deafness, tics, hyperactivity and autism spectrum disorders. Demyelinating changes in the white matter, atrophy of the brain and cerebellum have been described. Probands may have hypertelorism and a broad nasal root. Case report: A boy from the 1st pregnancy, without complications, delivered on time, by section, weight 2800 g, lenght 47 cm, normal postpartum adaptation. From infancy, he was monitored by a neurologist for hypotonia, retardation of verticalization and retardation of the expressive component of speech. For tics and autism under the care of a psychiatrist. The patient suffers from bizarre, purposeless movements, does not establish social and verbal contact, is profoundly autistic, only rarely makes a sound. His condition is assessed as severe mental retardation (IQ 30). At the age of 9, he was admitted to the University Hospital Brno for acute gastroenteritis with significant ion imbalance. Anthropometric parameters in the norm. The child was stigmatized (hypertelorism, wide root of the nose), hypotonic, did not speak, did not observe physical cleanliness, had diapers and did not make eye contact. Hearing examination (BERA) confirmed moderate perceptual deafness. MRI of the brain: random multiple foci of demyelinating character in the white matter, mainly in the paraventricular and juxtacortical zone, especially on the right parieto-occipitally merging into larger areas. As part of the differential diagnosis, the possibility of a hereditary metabolic disorder was considered, and a metabolic screening was performed. Profile of organic acids in urine: increased excretion of N-acetyl-alanine (27 mg/gKr), N-acetyl-glycine (23 mg/gKr), N-acetyl-methionine (78 mg/gKr), N-acetyl-glutamate (45 mg/gKr) and N-acetyl-valine (12 mg/gKr), which are not detected in urine under physiological conditions. The finding led to the suspicion of a possible deficiency of the ACY1D enzyme. DNA analysis of the ACY1 gene: the sequence variant NM_000666.2, c.1057C>T p.(Arg353Cys) was found in the homozygous state, which is the most frequently described pathogenic sequence variant for ACY1D. Conclusion: To date, most probands with ACY1D have been described in connection with children who underwent selective metabolic screening for psychomotor development delay and a history of seizures. Due to the low number of diagnosed cases, the clinical course of the disease cannot yet be predicted, the prognosis of patients remains unclear. The causal treatment is unknown. |