Diverse Clinical Presentation of RAC1-Related Intellectual Developmental Disorder.

RAC1 encodes the protein RAS-related C3 Botulinum Toxin Substrate 1 (RAC1), which plays a pivotal role in various cellular functions. Pathogenic variants in RAC1 are linked to the rare intellectual developmental disorder, autosomal-dominant 48 (MRD48). We present one case with typical phenotype and two cases with a mild phenotype.

Subtelomeric microdeletion in chromosome 20p13 associated with short stature.

Key Clinical Message: Among the total 10 reported cases with 20p13 microdeletion, including our patient, it is notable that 50% of patients presented a height below the 3rd percentile. We suggest that short stature is among the most common manifestations in patients with 20p13 subtelomeric microdeletion.

Abstract: Chromosome 20p13 microdeletion occurs rarely, with only 10 reported cases.

Maximal dietary responsiveness after tetrahydrobiopterin (BH4) in 19 phenylalanine hydroxylase deficiency patients: What super-responders can expect.

Background: Inherited phenylalanine hydroxylase deficiency, also known as phenylketonuria (PKU), causes poor growth and neurologic deficits in the untreated state. After ascertainment through newborn screen and dietary phenylalanine (Phe) restriction to achieve plasma Phe in the range of 120-360 μmol/L, these disease manifestations can be prevented. Poor compliance with protein restricted diets supported by medical food is typical in later years, beginning in the late toddler and teenage years.

Biochemical and molecular characteristics among infants with abnormal newborn screen for very-long-chain acyl-CoA dehydrogenase deficiency: A single center experience.

Objective: To define the biochemical and molecular characteristics and diagnostic outcomes of a large US cohort of VLCAD deficiency positive cases as detected by newborn screening (NBS) with MS:MS. This relatively common disorder of fatty acid oxidation is screened for in every state in America and often results in extensive testing of multiple samples to arrive at a diagnostic conclusion.

Materials And Methods: We compared NBS dried blood spot (DBS) acylcarnitine profile (ACP) C14, C14:1, C14:2, C14:1/C12:1 ratio and plasma C14, C14:1, C14:2, C14:1/C12:1, C14:1/C16 and C14:1/C2 ratios among true positive and false positive cases.

Genotype-phenotype correlation in IARS2-related diseases: A case report and review of literature.

Isoleucyl-tRNA synthetase 2 encodes mitochondrial isoleucine-tRNA synthetase. Pathogenic variants in the  gene are associated with mitochondrial disease. We report a female with compound heterozygous variants, p.

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency.

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects.

HSD10 disease in a female: A case report and review of literature.

HSD10 disease is a rare X-linked mitochondrial disorder caused by pathogenic variants in the gene. The phenotype results from impaired 17β-hydroxysteroid dehydrogenase 10 (17β-HSD10) protein structure and function. HSD10 is a multifunctional protein involved in enzymatic degradation of isoleucine and branched-chain fatty acids, the metabolism of sex hormones and neurosteroids, as well as in regulating mitochondrial RNA maturation.

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring.

Purpose: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age.

Bone manifestations in neuronopathic Gaucher disease while receiving high-dose enzyme replacement therapy.

Avascular necrosis (AVN), one type of bone infarction, is a major irreversible complication of Gaucher disease (GD). In this report, two pediatric patients with GD type 3, homozygous for the L483P pathogenic variant (formerly L444P), developed AVN despite treatment on long-term, high-dose enzyme replacement therapy (ERT). ERT was initiated in both patients, who had intact spleens, shortly after diagnosis with an initial dramatic response.

A Familial Case of Multicentric Carpotarsal Osteolysis Syndrome and Treatment Outcome.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability.

A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20 and TNFRSF13C.

Phelan-McDermid syndrome (PMS, OMIM 606232) is a heterozygous contiguous gene microdeletion syndrome occurring at the distal region of chromosome 22q13. This deletion encompasses the SHANK3 gene at 22q13.33, which is thought to be the critical gene for the neurodevelopmental features seen in this syndrome.

Novel de novo pathogenic variant in the NR2F2 gene in a boy with congenital heart defect and dysmorphic features.

The NR2F2 gene plays an important role in angiogenesis and heart development. Moreover, this gene is involved in organogenesis in many other organs in mouse models. Variants in this gene have been reported in a number of patients with nonsyndromic atrioventricular septal defect, and in one patient with congenital heart defect and dysmorphic features.

A case report of chromosome 17q22-qter trisomy with distinct clinical presentation and review of the literature.

Terminal 17q trisomy is very rare but a recognizable genetic syndrome. The majority of cases reported are inherited from a balanced translocation carrier. This syndrome involves many organs and the severity ranges from mild to severe depending on the size of the 17q gain.

Foramen magnum compression in Coffin-Lowry syndrome: A case report.

Coffin-Lowry syndrome (CLS) is a rare genetic disorder inherited in an X-linked dominant pattern. Common manifestations include intellectual disability, growth retardation, dysmorphic facial features, and variable skeletal anomalies. Here we report a patient who first presented with episodes of apparent life-threatening events (ALTE) found to be caused by hydrocephalus and brainstem compression at the foramen magnum.