"Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".

BACKGROUND: Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination. CLINICAL PRESENTATION: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation. CONCLUSIONS: In infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.

Unraveling Alström syndrome: Homozygous mutation c.2729C>G in ALMS1 gene across an extended family.

BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population. METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country. RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations. CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.

Renal angina index in critically ill children as an applicable and reliable tool in the prediction of severe acute kidney injury: Two tertiary centers' prospective observational study from the Middle East.

Acute kidney damage (AKI) is a common cause of pediatric intensive care unit (PICU) admissions. Implementing a reno-protective strategy for AKI prediction can significantly enhance outcomes. The renal angina index (RAI) is a risk stratification tool used to predict severe AKI. We aim to assess the reliability and accuracy of the RAI scoring system in predicting AKI as compared to other conventional AKI markers. A prospective, observational study was conducted in the PICU of 2 tertiary medical centers in the Middle East. A total of 446 patients, aged 1-month to 14-years, without chronic kidney disease were enrolled. The RAI was calculated using the renal risk and renal injury score within the first 8 to 12 hours of admission. The accuracy of RAI was compared to changes in serum creatinine from baseline. The outcome was assessed on Day 3 for presence of AKI according to the kidney disease improving global outcome (KDIGO) criteria and associated sequelae. A positive RAI (RA+) was defined as RAI readings ≥ 8. Among the patients, 89 (19.9%) had a positive RAI within the first 8 to 12 hours of admission. The RA + group had a significantly higher occurrence of Day 3 severe AKI (KDIGO stages 2&3) compared to the RA- group (60.6% vs 4.2%, P < .001). The RA + group also had a significantly higher utilization of renal replacement therapy (RRT) (21.3% vs 1.1%, P < .001), longer mean PICU length of stay in days (11.1 ±â€…3.5 vs 5.5 ±â€…2.1, P < .001), and increased mortality (31.4% vs 2.8%, P < .001) compared to the RA- group. The RAI score demonstrated superior predictive ability for Day 3 AKI, with a sensitivity of 72%, specificity of 95%, and area under the curve (AUC) of 0.837, compared to changes in serum creatinine from baseline (sensitivity: 65%, specificity: 89%, AUC: 0.773), fluid overload (sensitivity: 43.7%, specificity: 79%, AUC: 0.613), and illness severity scores (sensitivity: 52.4%, specificity: 80.5%, AUC: 0.657). RAI proved to be a reliable and rapid bedside test for identifying critically ill children at risk of developing severe AKI. This enables physicians to implement reno-protective measures and intervene early, thereby improving prognosis.

Vertebral artery dissection aneurysm in a pediatric patient: A rare case with unusual clinical manifestations, diagnostic, and management challenges.

Vertebral artery aneurysm is a rare condition with diverse clinical manifestations in pediatric patients. We present the case of a 12-year-old male who presented with diplopia, vomiting, ataxia, and severe headache. Diagnostic evaluation revealed an extracranial vertebral artery dissection with an associated aneurysm at the C3-C4 level. Despite the absence of recurrent ischemic strokes, the aneurysm posed challenges in differentiating the symptoms from other inflammatory demyelinating disorders, particularly internuclear ophthalmoplegia. Diagnosis relied on a thorough history, physical examination, and imaging studies. Magnetic resonance imaging with magnetic resonance angiography confirmed the diagnosis and played a crucial role in assessing the size, location, and extent of the aneurysm. Additionally, the imaging findings helped guide treatment decisions and determine the need for anticoagulation therapy. Regular follow-up imaging was initiated to monitor for late complications and evaluate the effectiveness of the management approach. This case highlights the atypical presentation of vertebral artery aneurysm in a pediatric patient, underscoring the importance of clinical suspicion and the role of advanced imaging techniques in facilitating accurate diagnosis and guiding appropriate management. Prompt diagnosis and optimal utilization of imaging modalities are essential in preventing severe morbidity and mortality. Further research is warranted to enhance our understanding of this condition and refine imaging and management protocols in pediatric population.

Case Report: Dubin-Johnson Syndrome Presenting With Infantile Cholestasis: An Overlooked Diagnosis in an Extended Family.

Dubin-Johnson syndrome (DJS) is an often-missed diagnosis of neonatal cholestasis. We report two patients with DJS, who presented with neonatal cholestasis. The first patient underwent extensive investigations for infantile cholestasis with no definitive etiology reached; the diagnosis of DJS was missed until the age of 14 years old. The diagnosis was confirmed genetically with c.2273G > T, p.G758V mutation in exon 18 of the ABCC2 gene. The 2nd patient is a 7-day-old baby, the son of the 1st patient who gave birth to him at the age of 21 years old. He was diagnosed with DJS at the age of 2 weeks based on normal clinical and laboratory workup apart from direct hyperbilirubinemia. He had the same mutation as his mother in homozygous status. The husband was heterozygous for the same mutation. DJS is one of the often-missed differential diagnoses of neonatal cholestasis. It should be suspected in patients of infantile cholestasis, who have an, otherwise, normal physical examination, and laboratory investigations to avoid unnecessary lengthy, invasive, and expensive workups.