Dataset Information

Aminoacylase 1 deficiency: case report on three affected siblings.

ABSTRACT:

Background

Aminoacylase 1 (ACY1, EC 3.5.1.14) deficiency (ACY1D) is a very rare inherited metabolic disease (IMD) with autosomal recessive inheritance (OMIM #609924). Up to date, only 15 cases have been reported in the literature. It is diagnosed by detecting acetylated amino acids among the patient's urine organic acids by gas chromatography-mass spectrometry. Its clinical manifestations are highly variable, ranging from severe neurological symptoms to being asymptomatic.

Case description

We present a 14-year-old boy with mild intellectual disability, speech sound disorder and non-alcoholic fatty liver disease who exhibited increased urinary excretion of N-acetylalanine, N-acetylmethionine and N-acetylglutamine during testing for inherited metabolic disorders. A suspected ACY1D was subsequently confirmed by targeted next generation sequencing, which revealed the presence of a homozygous pathogenic missense mutation in the ACY1 gene, c.1057C>T (p.Arg353Cys). The proband underwent speech education with good outcome. The same homozygous mutation in ACY1 gene was found in the boy's two brothers, who exhibited slightly varied intellectual abilities. Follow-up examinations of the siblings revealed no deterioration in their mental skills.

Conclusions

These results suggest that uneven mental abilities in pediatric patients with various disorders including autism spectrum disorder may be sufficient grounds to warrant metabolic testing for ACY1D. The acylglycines urine excretion could be a promising novel metabolic marker for ACY1D testing.

SUBMITTER: Smolka V

PROVIDER: S-EPMC10789890 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Aminoacylase 1 deficiency: case report on three affected siblings.

Smolka Vratislav V Friedecky David D Kolarova Jana J Tkacik Oksana O Foltenova Hana H Bekarek Vojtech V Vrtel Petr P Srovnal Josef J

AME case reports 20231211

<h4>Background</h4>Aminoacylase 1 (ACY1, EC 3.5.1.14) deficiency (ACY1D) is a very rare inherited metabolic disease (IMD) with autosomal recessive inheritance (OMIM #609924). Up to date, only 15 cases have been reported in the literature. It is diagnosed by detecting acetylated amino acids among the patient's urine organic acids by gas chromatography-mass spectrometry. Its clinical manifestations are highly variable, ranging from severe neurological symptoms to being asymptomatic.<h4>Case descri ...[more]

PMID: 38234346

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Project description:BackgroundLPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient's presentation with a reviewed synthesis of the available literature.Case presentationsThe younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic-clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla. His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions.ConclusionsNeurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.

Project description:BackgroundCongenital adrenal hyperplasia (CAH) due to steroid 11β-hydroxylase deficiency (11β-OHD) is a rare form of CAH associated with low renin hypertension, hypokalemia, hyperandrogenemia and ambiguous genitalia in affected females. Herein we describe the clinical, hormonal and molecular characteristics of two Uzbekistan siblings with 11β-OHD and analyze the effects of a splicing mutation.Case presentationA 46,XX girl presented with genital ambiguity and low renin hypertension; her 46,XY brother presented with precocious puberty. Hormonal studies suggested 11β-OHD. Mutation analysis was performed by PCR followed by Sanger sequencing of the entire coding regions and their flanking introns of the CYP11B1 gene. Mutation analysis showed that both patients were compound heterozygous for IVS7 + 1G > A, and c.421C > T. Although the identified mutations have been previously described, this is, to our knowledge, the first report of these mutations in compound heterozygotes. A minigene assay was used to determine the effects of the splicing mutation. The constructs containing either the wild-type or the splice-site mutant CYP11B1 genomic DNA of exons-introns 6-9 were transfected into COS-7 cells; subsequently, RNA splicing was assessed by reversed transcribed-PCR of CYP11B1 complementary DNA. The minigene assay revealed that the IVS7 + 1G > A mutation resulted in two shorter incorrectly spliced products; one skipping the exon 7 and the other skipping the exons 7-8. The c.421C > T mutation leads to the introduction of a premature stop codon at residue 141 (p.R141X). These mutations are expected to code non-functional proteins.ConclusionCompound heterozygous mutations (IVS7 + 1G > A and p.R141X) in the CYP11B1 gene were found to cause 11β-OHD. The IVS7 + 1G > A mutation causes aberrant splicing of CYP11B1 leading to exon skipping. This finding could facilitate the future novel therapies targeted on splicing modulation to treat human disease.

Dataset Information

Aminoacylase 1 deficiency: case report on three affected siblings.

Background

Case description

Conclusions

Publications

Aminoacylase 1 deficiency: case report on three affected siblings.

Similar Datasets

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