RESUMEN

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis. Upon admission, gastroscopy revealed esophageal and gastric varices. Abdominal CT scan, MRI, and color Doppler ultrasound suggested cirrhosis, intrahepatic bile duct dilation, and bilateral kidney enlargement. Genetic testing identified compound heterozygous mutations in the PKHD1 gene: c.2264C>T (p.Pro755Leu) and c.1886T>C (p.Val629Ala). The c.2264C>T (p.Pro755Leu) mutation is a known pathogenic variant with previous reports, while c.1886T>C (p.Val629Ala) is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2. The child was diagnosed with autosomal recessive polycystic kidney disease. In children presenting with gastrointestinal bleeding without obvious causes, particularly those with liver or kidney disease, consideration should be given to the possibility of autosomal recessive polycystic kidney disease, and genetic testing should be conducted for definitive diagnosis when necessary.

Asunto(s)

RESUMEN

Mucopolysaccharidosis (MPS) consists of a heterogeneous group of multisystem disorders that are usually inherited. This spectrum consists of seven subtypes in total. Sly syndrome, also known as type VII MPS, is a multisystem disorder with a wide array of symptoms that overlap with other mucopolysaccharide disorders. Diagnosis of Sly syndrome relies on metabolic and radiological criteria. This report presents a case of a 19-year-old male who presented with seizures as his chief complaint. By metabolic workup done previously, he was diagnosed with Sly syndrome, an autosomal recessive mucopolysaccharide syndrome. This case underscores various multisystem features associated with the disease; however, it mainly highlights and emphasizes the diverse neurological features, including typical and atypical neuroimaging in Sly syndrome, aiding in its characterization, early diagnosis, and management.

RESUMEN

Human SULT2B1gene is responsible for expressing SULT2B1a and SULT2B1b enzymes, which are phase II metabolizing enzymes known as pregnenolone and cholesterol sulfotransferase (SULT), respectively. They are expressed in several tissues and contribute to steroids and hydroxysteroids homeostasis. Genetic variation of the SULT2B1 is reported to be associated with various pathological conditions, including autosomal recessive ichthyosis, cardiovascular disease, and different types of cancers. Understanding the pathological impact of SULT2B1 genetic polymorphisms in the human body is crucial to incorporating these findings in evaluating clinical conditions or improving therapeutic efficacy. Therefore, this paper summarized the most relevant reported studies concerning SULT2B1 expression, tissue distribution, substrates, and reported genetic polymorphisms and their mechanisms in enzyme activity and pathological conditions.

RESUMEN

We report a case of dilated cardiomyopathy-like hypertensive cardiomyopathy (HTN-CM) with polycystic kidney disease without family history when a 3-month-old boy developed bacteraemia secondary to a urinary tract infection. He was later confirmed as having autosomal recessive inheritance due to the proven PKHD1 gene mutation. The treatment consisted mainly of antihypertensive and anti-heart failure therapies and he was discharged on the 131st day. To prevent the development of heart failure in patients with HTN-CM due to autosomal recessive polycystic kidney disease (ARPKD), it is important to improve the fetal diagnosis rate of ARPKD, detect hypertension early, and strictly control the blood pressure after birth.

RESUMEN

BACKGROUND AND OBJECTIVES: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) has recently been known as HTRA1-related cerebral small-vessel disease (CSVD), it is caused by variants in HTRA1. Recently, it has been reported to develop in heterozygotes with some variants of the gene. Multiple prospective studies have reported that the frequency of heterozygous HTRA1 variants developing CSVD is 2 - 6.5 % in CARASIL. Heterozygous variant cases lack unique clinical features, have an older age of onset, and are difficult to detect. Characteristic findings are required to identify such cases. METHOD: Magnetic resonance imaging (MRI) images of cases that experienced cerebral infarction and carried heterozygous variants in HTRA1 were reviewed. RESULTS: Four cases of heterozygous HTRA1-related CSVD in two families (Family 1: c.754G > A, p.A252T; three males. Family 2: c.497G > T, p.R166L, one female). In all cases, white matter lesions with lacunar infarcts were observed in the periventricular and basal ganglia, external capsule, and brainstem. Moreover, T2 star weighted image (T2*WI) low presented dot-like lesions were present along the surface of the brainstem, which have only been reported in one homozygous case. Susceptibility-weighted imaging (SWI) was performed in two cases, and the dot-like lesions on T2*WI resembled a pearly tiara along the surface of the brainstem. CONCLUSION: Brainstem surface on T2*WI low showed dot-like lesions, which are not generally observed in patients with stroke and can be characteristic of HTRA1-CSVD associated with heterozygous variant. The pathology requires further investigation for diagnosis.

RESUMEN

INTRODUCTION: In the present study we describe atypical cases with bright and enlarged fetal kidneys identified on fetal ultrasound with different genetic etiologies. METHODS: Exome sequencing was undertaken after prenatal counseling and after the initial diagnosis of enlarged fetal kidneys was made on ultrasound for four cases and the results were then correlated. RESULTS: In the present study we identified underlying variants in ACE, ETFA, PKD1, and MKS1 gene where the atypical presentation of fetal kidneys was noted either as a part of spectrum of syndrome or alone. CONCLUSIONS: In the era of exome sequencing, targeted gene sequencing is getting replaced and for better. However not all answers are direct, and sometimes the variant categorization is dependent on the acumen and agreement of all those involved in the process. It includes those involved the diagnostic as well those catering to the patients. It is very important to be updated on the relevance of multiple gene in causing similar phenotypes particularly in the prenatal context were coming up with a timely diagnosis is very important for any sort of intervention.

RESUMEN

Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) have significant phenotypic overlap and a similar genetic background, both caused mainly by variants in sarcomeric genes. HCM is the most common cardiomyopathy, while RCM is a rare and often underdiagnosed heart condition, with a poor prognosis. This study focuses on a large family with four infants diagnosed with fatal RCM associated with biventricular hypertrophy. Affected infants were found to be homozygous for NM_003280.3(TNNC1):c.23C>T(p.Ala8Val) variant. Interestingly, this variant resulted in a low penetrance and mild form of hypertrophic cardiomyopathy (HCM) in relatives carrying a single copy of the variant. Overall, this study underscores the complex nature of genetic inheritance in cardiomyopathies and the wide range of clinical presentations they can exhibit. This emphasizes the vital role of genetic testing in providing essential insights crucial for diagnosis, prognosis, early intervention, and the development of potential treatment strategies.

RESUMEN

Introduction: Riboflavin transporter deficiency type 2 (RTD2) is a rare neurodegenerative autosomal recessive disease caused by mutations in the SLC52A2 gene encoding the riboflavin transporters, RFVT2. Riboflavin (Rf) is the precursor of FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), which are involved in different redox reactions, including the energetic metabolism processes occurring in mitochondria. To date, human induced pluripotent stem cells (iPSCs) have given the opportunity to characterize RTD2 motoneurons, which reflect the most affected cell type. Previous works have demonstrated mitochondrial and peroxisomal altered energy metabolism as well as cytoskeletal derangement in RTD2 iPSCs and iPSC-derived motoneurons. So far, no attention has been dedicated to astrocytes. Results and discussion: Here, we demonstrate that in vitro differentiation of astrocytes, which guarantee trophic and metabolic support to neurons, from RTD2 iPSCs is not compromised. These cells do not exhibit evident morphological differences nor significant changes in the survival rate when compared to astrocytes derived from iPSCs of healthy individuals. These findings indicate that differently from what had previously been documented for neurons, RTD2 does not compromise the morpho-functional features of astrocytes.

RESUMEN

Background: HMGXB4 (additionally known as HMG2L1) is a non-histone DNA-binding protein that contains a single HMG-box domain. HMGXB4 was originally described in Xenopus where it was seen to negatively regulate the Wnt/ß-catenin signaling pathway. Materials and methods: In this study, we conducted a genetic and clinical evaluation of a single family with three affected individuals suffering from intellectual disability (ID), global developmental delay (GDD) and dysmorphic facial features.Whole genome sequencing (WGS) and Sanger sequencing were performed on the affected individuals' DNA to identify genetic variations. Additionally, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess gene expression in both the affected and unaffected individuals in the family. Result: WGS identified a homozygous frameshift variant c.1193_1196del p. (Lys398Argfs × 25) in exon 5 of the HMGXB4 gene (OMIM 604702), which completely segregated the disease phenotype in the family. Furthermore, RT-qPCR revealed a substantial decrease in the HMGXB4 gene expression in the affected individuals as compared to the unaffected individuals of the family. Conclusions: The current study is the first evidence linking a genetic variant in the HMGXB4 gene to ID, GDD, and dysmorphic facial features. Therefore, it is possible that HMGXB4 contributes significantly to developmental milestones and may be responsible for neurodevelopmental disorders in humans.

RESUMEN

Homozygous mutations in the lipopolysaccharide-responsive vesicle trafficking, beach- and anchor-containing (LRBA) gene lead to a syndrome characterized by early-onset hypogammaglobulinemia, autoimmunity, lymphoproliferation, and inflammatory bowel disease. This report describes a 10-year-old female who experienced three seizure episodes, including two generalized tonic-clonic seizures (GTCS) and one focal seizure, alongside septic shock. The patient had a history of recurrent respiratory tract infections, inflammatory bowel disease, multiple blood transfusions, lymphadenopathy, significant organomegaly, and hematological abnormalities, all consistent with an LRBA deficiency. This case highlights the critical need for prompt recognition and identification of LRBA gene mutations to enable timely management and improve patient outcomes.

RESUMEN

Seckel syndrome, also commonly called Seckel dwarfism, is a rare congenital disorder and always associated with severe growth retardation in utero. This retarded growth lingers on and causes serious developmental deformities ensuing to short stature, microcephaly, mental retardation, and a beak-like nose. This case report intends to present an interesting case of a 14-year-old female patient with various clinical manifestations, typical radiographic features, and characteristic dental manifestations correlated with the literature. A detailed understanding of the present case would assist pediatric dentists in correct and prompt diagnosis, precise treatment, and the prevention of severe consequences caused by Seckel syndrome. How to cite this article: Tatiya N, Kesri R, Ukey A. Seckel Dwarfism-A Rare Autosomal Recessive Inherited Syndrome: A Case Report. Int J Clin Pediatr Dent 2024;17(2):211-215.

RESUMEN

The clotting pathway involves intrinsic and extrinsic pathways converging into a common pathway. These pathways require activated factors that sequentially convert prothrombin to thrombin, which then converts fibrinogen to fibrin, forming a stable clot. Clotting factor deficiency impairs this cascade leading to excessive bleeding or bruising due to insufficient clot formation. Here, we present the case of a 47-year-old female who initially complained of epigastric pain. By the third day of admission, she experienced four to five episodes of bleeding gums, resulting in a blood loss of approximately 300 mL. The patient exhibited abnormal prothrombin time (PT) and international normalized ratio (INR) values, leading to a diagnosis of Factor X (FX) deficiency upon further evaluation. This case report emphasizes the need to diagnose coagulopathies such as FX deficiency and how early diagnosis will help not only in patient care and management but also in screening family members who may be affected.

RESUMEN

Glanzmann thrombasthenia and clotting factor VII deficiency are rare autosomal recessive bleeding disorders. But the occurrence of both in the same person is an extremely rare phenomenon. Here, we present the case of a young female from Sindh, Pakistan that got diagnosed with Glanzmann thrombasthenia and concomitant moderate factor VII deficiency, a combination not previously reported in the country. The patient exhibited typical clinical manifestations including menorrhagia, nasal bleeds, and prolonged bleeding after minor injuries, compounded by a positive family history and consanguinity. Laboratory investigations revealed marked anemia, prolonged bleeding time, and abnormal platelet aggregation studies consistent with Glanzmann thrombasthenia. The identification of this rare combination relied on comprehensive clinical evaluation, emphasizing the importance of family history in suspected cases. Management involved platelet transfusions, tranexamic acid, and Factor VII replacement, resulting in clinical improvement.

RESUMEN

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.

Asunto(s)

RESUMEN

Sequence variants in Eyes Shut Homolog (EYS) gene are one of the most frequent causes of autosomal recessive retinitis pigmentosa (RP). Herein, we describe an Italian RP family characterized by EYS-related pseudodominant inheritance. The female proband, her brother, and both her sons showed typical RP, with diminished or non-recordable full-field electroretinogram, narrowing of visual field, and variable losses of central vision. To investigate this apparently autosomal dominant pedigree, next generation sequencing (NGS) of a custom panel of RP-related genes was performed, further enhanced by bioinformatic detection of copy-number variations (CNVs). Unexpectedly, all patients had a compound heterozygosity involving two known pathogenic EYS variants i.e., the exon 33 frameshift mutation c.6714delT and the exon 29 deletion c.(5927þ1_5928-1)_(6078þ1_6079-1)del, with the exception of the youngest son who was homozygous for the above-detailed frameshift mutation. No pathologic eye conditions were instead observed in the proband's husband, who was a heterozygous healthy carrier of the same c.6714delT variant in exon 33 of EYS gene. These findings provide evidence that pseudodominant pattern of inheritance can hide an autosomal recessive RP partially or totally due to CNVs, recommending CNVs study in those pedigrees which remain genetically unsolved after the completion of NGS or whole exome sequencing analysis.

Asunto(s)

RESUMEN

Deficiency of adipose triglyceride lipase (ATGL) due to mutation in PNPLA2 causes neutral lipid storage disease with myopathy (NLSDM), an autosomal recessive disorder (MIM: #610717). NLSDM patients are mainly affected by progressive myopathy, cardiomyopathy, and hepatomegaly. Cardiac involvement was reported in 40%-50% of NLSDM patients. Patients with cardiac involvement have adult-onset progressive heart failure, mimicking dilated or hypertrophic cardiomyopathy. The clinical characteristics, genotype-phenotype correlation, and prognosis of cardiomyopathy secondary to PNPLA2 mutation are not understood. We reported two male patients carrying a homozygous splicing mutation NM_020376.4 (c.757 + 1G>T) in PNPLA2, presenting with severe dilated cardiomyopathy and mild skeletal muscle involvement. Through the literature review, the ECG and imaging features and the prognosis of 49 previously reported cases of cardiomyopathy caused by the PNPLA2 mutation were summarized. This study suggests that NLSDM should be considered a cause of cardiomyopathy, especially in those with elevated creatine kinase (CK) levels, regardless of whether symptoms such as muscle weakness or atrophy are present.

RESUMEN

Purpose: To report the retinal findings in a patient with autosomal recessive spastic ataxia of Charlevoix-Saguenay. Methods: A case was evaluated. Results: A 16-year-old male patient with a known diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay was referred for evaluation of retinal hypermyelination given its frequent association with the condition. The patient was asymptomatic with a best-corrected visual acuity of 20/20. Optical coherence tomography of the peripapillary retinal nerve fiber layer (RNFL) showed bilateral thickening in each eye (average thicknesses: 180 µm, right eye; 177 µm, left eye). An examination showed no myelinization of the RNFL. Conclusions: Most studies to date describe RNFL thickening secondary to hypermyelination as a characteristic finding in autosomal recessive spastic ataxia of Charlevoix-Saguenay. This case provides evidence that this thickening may be a result of hypertrophy rather than hypermyelination. Further investigation is needed to define the pathophysiologic cause of RNFL thickening in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

RESUMEN

Primary renal hypouricemia (RHUC) is a rare autosomal recessive disorder with a mean duration of end-stage acute kidney injury (EIAKI) of 14 days. The pathogenesis of EIAKI in patients with RHUC remains unclear. Several hypotheses have been proposed, including those related to the renal vasoconvulsive effect and the elevating effect of xanthine oxidase (XO). The effect of xanthine oxidase (XO) is most often observed following strenuous anaerobic exercise, which is frequently accompanied by low back pain, nausea, and acute kidney injury (AKI). Consequently, we postulate that EIAKI could be prevented by avoiding strenuous exercise, thus preventing the onset and recurrence of EIAKI. In this paper, we present a case of recurrent EIAKI in a patient with RHUC and a mutation in the SLC2A9 gene.

Asunto(s)