Saudi Boy Research Articles

HGG-01. DURABLE RESPONSE TO IMMUNOTHERAPY IN AN ADOLESCENT PATEINT WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY CMMRD AND SYNCHRONOUS THREE PRIMARY MALIGNANCIES

Abstract BACKGROUND Familial Cancer Syndrome FCS is of particular concern in Saudi Arabia due to the high rates of consanguinity. Constitutional mismatch repair deficiency Syndrome (CMMRD) is an autosomal recessive FCS with a wide spectrum of malignancies Caused by Biallelic germline mutations in one of 4 mismatch repair genes (MLH1, PMS2, MSH2, and MSH6). METHODS we report 13 yr. Saudi boy, previously healthy with multiple café-au-lait (CAL) macules, and Consanguineous parents with a positive family history of Malignancy. presented with progressive headache, vomiting, abdominal pain, weight loss, and microcytic anemia. MRI Brain showed a Large left hemispheric necrotic mass, MRI abdomen: Circumferential gastric body wall thickening Distal transverse colon intraluminal polypoid mass, and liver hypodense lesion. He had a Resection of the brain tumor and Upper GI endoscopy + colonoscopy with polypectomy: which showed an Ugly gastric ulcer, and multiple colonic polyps. RESULTS Brain tumor molecular pathology: Gliosarcoma WHO grade 4 with negative IHC expression in PMS2 protein, hypermutant tumor with somatic PMS2 ATRX, TP53, NFI, and PIK3R1 genes mutation. stomach biopsy confirmed invasive gastric adenocarcinoma and Colonic polyp biopsy: Tubulovillous adenoma. Genetic testing Detect pathogenic Biallelic germline PMS2 mutation. He received adjuvant focal Brain radiation therapy 59.4Gy/33 F concurrent with immunotherapy (PD-1) inhibitor Nivolumab. Follow-up Abdominal imaging showed excellent response to immunotherapy with no significant residual lesion. MRI of the brain showed surgical bed multi-cystic lesions with thick nodular enhancement suggestive either of radiation necrosis vs. progressions/pseudoprogression. repeated MRI confirmed further progression of the enhancing surgical cavity lesion which was unresectable. CTLA-4 Inhibitor ipilimumab was added to Nivolumab to optimize therapy. UpToDate our patient is clinically stable on Maintenance Nivolumab with no side effects. CONCLUSION Our case confirms immunotherapy’s efficacy for treating CMMRD-related cancers, which can improve survival while reducing toxicity from less effective conventional therapies.

RIDDLE syndrome ring finger protein 168 deficiency in a 9-month-old boy from Jazan, Saudi Arabia

This study explores the intricate challenges of ring finger protein 168 (RNF168) deficiency, an uncommon genetic disorder characterized by immunodeficiency, radiation sensitivity, and diverse clinical traits. Presenting the case of a 9-month-old Saudi boy, our investigation emphasizes the critical importance of early diagnosis and intervention in managing this complex syndrome. Comparative analyses across global cases reveal substantial diversity in clinical features and genetic profiles, underscoring the need for ongoing research and international collaboration. Our findings significantly contribute to the understanding of RNF168 deficiency, guiding diagnostic and management strategies for improved patient outcomes. While acknowledging study limitations, particularly in comprehensive assessments, this research highlights the necessity for continued exploration to unravel the genetic and clinical intricacies of RNF168 deficiency. The insights gained from this study hold the potential for advancing knowledge and refining approaches to diagnose and manage this rare disorder effectively.

A novel mutation in TANGO2 gene associated with recurrent muscle weakness with rhabdomyolysis , metabolic encephalopathy and cardiac arrhythmia: a case report

Background TANGO2 depletion was found to cause clinically recognizable multi-organ involvement disorder in pediatrics with episodic muscle weakness recurrent rhabdomyolysis, intellectual disability, metabolic encephalomyopathic crises and cardiac arrhythmia. TANGO2 deficiency is also referred to as \"metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration\" (MECRCN) in OMIM. * 616830 Case presentation We report a case of a 4-year-old Saudi boy from a consanguineous Saudi family with two uncles deceased at 3 year of age with recurrent muscle weakness and hyperammonemia of unknown cause .Patient in last attack progressed to severe metabolic encephalomyopathic crisis that required assisted ventilation for 4 months, complicated with life threatening cardiac tachyarrhythmia. Laboratory findings of hypoglycemia, mild hyperammonemia , severely elevated plasma Creatine Kinase, myoglobinuria , lactic acidosis and increased TSH concentration indicating hypothyroidism have been documented. The clinical profile was highly suggestive of TANGO2-realted disorder. Direct DNA sequence analysis of the entire coding regions of TANGO2 gene identified a novel homozygous deletion for three nucleotides in exon 2 (c.11_13delTCT) resulting in amino acid deletion (phenylalanine) at position 5. Conclusion This report illustrates the importance of collating clinical data and keeping a high index of suspicion in order to reach to the diagnosis.

Cherubism in Saudi population: a rare case report

Cherubism is a rare hereditary benign fibro-osseous disorder characterised by bilateral swelling of the mandible and/or maxilla with varying severity of involvement. It occurs because of dominant mutations in SH3BP2 gene on the chromosome 4p16.3. On radiography cherubic lesions appear as multilocular cystic radiolucencies in the jaw bones giving a soap bubble appearance. These lesions usually heal by themselves by the time the patient attains puberty. Treatment is necessary only in aggressive cases where there is severe facial deformity or vital functions are hampered. Surgical corrections are preferred when the lesion is in its dormant phase. The aim of the present case report is to illustrate a case of cherubism in a 9-year-old Saudi boy which is a very rare occurrence as only 1 case of cherubism has been reported so far in the Saudi Arabian population. KEYWORDS Cherubism; Genetic mutation; Multilocular cystic lesions; Self-regressive lesion; Calcitonin therapy.

Undiscovered Phenotype of KARS1 Related Mitochondrial Leukoencephalopathy

Background: Infantile onset progressive leukoencephalopathy with or without deafness is an autosomal recessive neurodegenerative disorder with variable clinical presentation, manifesting in infancy or early childhood. This disorders is one of KARS1 gene mutation spectrum that results mostly from compound heterozygous mutations rather than homozygous mutations, resulting in a dysfunctional mitochondrial enzyme. Case presentation: We report our 4-year-old Saudi boy of non-consanguineous parents, with a compound heterozygous mutation in KARS1 gene presenting clinically with speech delay, bilateral sensonural hearing loss, unilateral progressive hemiparesis, iron deficiency anemia and lytic bone lesions. Conclusion: KARS1 mutation has a heterogenous phenotypic presentation, and variable clinical severity. We report a new clinical feature of lytic bone lesions which could potentially expand the phenotype of this genetic disorder spectrum. Early recognition of the clinical presentation is warranted to facilitate diagnosis, prognosis and appropriate family counseling.

PMON311 45,X/46,XY mixed gonadal dysgenesis: a case report from Saudi Arabia

Abstract Introduction Mixed gonadal dysgenesis is a sex developmental disorder where the gonads are abnormal from there being some cells with XY chromosomes and some with just asingle X, known as chromosome Y mosaicism. This results in a wide range of male/female genitalia that are not typically, or clearly, male or female The case: 3 years old Saudi boy was born term to 35 year old G5P5 Normal anti natal and history of consanguinity. Birth weight 2 kilogram and found to have genital ambiguity in the form of short phallus structure and hypospiadius testis were felt at the right inguinal canal. his investigation showed abnormal chromosomes 45×46XY musiac . Mother chromosomes were 46XX normal female karyotype. normal siblings and Wes WES: CNV DESCRIPTION*: seq[GRCh37] Yp11.31q11.23 (mosaic∼50% of the cells) SIZE (KB): ∼26Mb, GENE COUNT**: 116, INTERPRETATION***: Pathogenic. RELATED DISORDER: 45,X/46,XY mixed gonadal dysgenesis The radiological investigations showed small oval shaped mass over the right inguinal canal 0.8/0.6/0.8 cm in size .the left testis couldn't be seen . And Genetogram showed presence of vagina and small uterus. his laboratory investigations showed at age of 2.5 years LH: less than o.3 and his Testosterone basal was less than 0.09 and Testosterone post HCG 8.29 which should excellent response to HCG.. the case was discussed with the paediatric urologist and the decision was as per the anatomical finding and results of the stimulated Testosterone to give Testosterone injections and asses the response. The child respond very well to the testosterone treatment which leads to improvement in the size and length of the phallus. Discussion mixed gonadal dysgenesis is one of the causes of DSD .45, X/ 46, XY mosaic: At birth around 90 per cent of babies with 45,X/46,XY have normal-appearing external male genitals, five per cent have normal-appearing female genitals and in five percent the external reproductive organs are neither fully male nor fully female. They may find one or two gonads that are very inadequate testes, possibly with some ovary-like tubules present. They may find one streak gonad and one immature, dysgenetic or normal testis. They may find an internal vagina, cervix and uterus, although these are usually quite small compared to a normal female. Some people with a 45,X/46,XY karyotype have reduced fertility and some are infertile. No judgment can be made about fertility until well after puberty in the apparently normal males. Children with a 45,X/46,XY karyotype can have any of the medical conditions that are more common among girls with Turner syndrome (who have a 45,X karyotype), which includes heart and disorders, autoimmune disorders and short stature. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Pediatric intussusception due to basidiobolomycosis: a case report and literature review

BackgroundPediatric gastrointestinal basidiobolomycosis is an unusual fungal infection caused by Basidiobolus ranarum, an environmental saprophyte found worldwide. Typically, basidiobolomycosis presents as a subcutaneous infection or soft tissue tumor-like lesion, and rarely involves the gastrointestinal tract. Gastrointestinal basidiobolomycosis is most common in young infants. It has no definitive clinical presentation, and almost all cases are misdiagnosed during the initial presentation.Case presentationWe report the case of a 4-year-old Saudi boy who presented to the emergency department with abdominal pain, nausea, vomiting, and weight loss. Ultrasonography revealed a target sign. Based on the ultrasonography findings, surgery was performed, which revealed the presence of intussusception. Eventually, the patient was diagnosed with intussusception secondary to intra-abdominal basidiobolomycosis based on the histological findings. The patient was readmitted and intravenous voriconazole therapy was initiated. One week after the second admission, the patient developed abdominal pain, nausea, vomiting, inability to hold down food, and constipation. Computed tomography of the abdomen was suggestive of small bowel obstruction, which was managed conservatively. The patient responded well and was subsequently discharged with a prescription of oral voriconazole.ConclusionsThis case reveals that gastrointestinal basidiobolomycosis can cause intussusception. This report will inform clinicians of the importance of considering gastrointestinal basidiobolomycosis in the differential diagnosis of chronic abdominal pain in children, even in the absence of fever or a clinically obvious abdominal mass, especially in countries such as Saudi Arabia, where cases have been reported.

Early recognition and treatment of TC II deficiency

Background: Transcobalamin (TC) is a carrier protein and it delivers vitamin B12 to the cellular TC receptor. TC II deficiency is a very rare disease and is life-threatening if left untreated. It is an Autosomal recessive disease and needs lifelong treatment. The clinical presentations are variable, started at early infancy, and sometimes mimic severe combined immunodeficiency or acute leukemia. It includes failure to thrive, diarrhea, anemia and or pancytopenia, hypotonia, developmental delay, and recurrent infection. Diagnosis of TC II deficiency is suspected based on clinical presentations with megaloblastic anemia, the elevation of plasma homocysteine, and urine methylmalonic acid level with a normal vitamin B12 and folate level. Molecular analysis of the TCN 2 gene is needed for confirmation of the diagnosis. Case Presentation: We present a case of 2 years old Saudi boy who was admitted to the hospital with a history of fever, recurrent chest infection, failure to thrive with diarrhea, and hypotonia, and his complete blood counts showed Pancytopenia. Though, normal vitamin B12 level and folate level, homocysteine, and urine methylmalonic acid lever were elevated. Peripheral smear and bone marrow aspiration and biopsy revealed Hypersegmented neutrophils and megaloblastic change.

Early recognition and treatment of TC II deficiency

Transcobalamin (TC) is a carrier protein and it delivers vitamin B12 to the cellular TC receptor. TC II deficiency is a very rare disease and is life-threatening if left untreated. It is an Autosomal recessive disease and needs lifelong treatment. The clinical presentations are variable, started at early infancy, and sometimes mimic severe combined immunodeficiency or acute leukemia. It includes failure to thrive, diarrhea, anemia and or pancytopenia, hypotonia, developmental delay, and recurrent infection. Diagnosis of TC II deficiency is suspected based on clinical presentations with megaloblastic anemia, the elevation of plasma homocysteine, and urine methylmalonic acid level with a normal level of vitamin B12 and folate. Molecular analysis of the TCN 2 gene is needed for confirmation of the diagnosis. We present a case of 2 years old Saudi boy who was admitted to the hospital with a history of fever, recurrent chest infection, failure to thrive with diarrhea, and hypotonia, and his complete blood counts showed Pancytopenia. Though, normal vitamin B12 level and folate level, homocysteine, and urine methylmalonic acid lever were elevated. Peripheral smear and bone marrow aspiration and biopsy revealed Hypersegmented neutrophils and megaloblastic change.

Furuncular myiasis by Wohlfahrtia magnifica (Diptera: Sarcophagidae) in a healthy child

Rationale: Human myiasis is the invasion of tissue or organs by fly larvae. This could be obligatory, facultative, or accidental.Patient concerns: A 4-year-old Saudi boy complained of fever over the past three days with multiple inflamed painful dermal furuncles and worms-like discharge.Diagnosis: Furuncular obligatory myiasis caused by Wohlfahrtia magnifica.Interventions: Maggots were removed for identification. The wounds were cleaned with antiseptic dressings. Topical and oral antibiotics were applied.Outcomes: Seven days later, the wounds completely healed.Lessons: Although several reports correlated human myiasis with old age, low health status, mental retardation, and low socioeconomic status, but the patient in our case was a healthy child from a family with good socioeconomic status, good hygiene, no history of diseases or mental disability, but traveled to a village where the climate is suitable for fly breeding.

Traumatic Aortic Injury in a 3-Year-Old Child - A Case Report and Literature Review

This case report describes a case of aortic injury with pseudo-aneurysm in a 3-year-old Saudi boy following a motor vehicle accident. The diagnosis was suspected on computed tomography scan, and emergency surgery was performed. A Dacron graft was inserted to repair the injured aorta. Postoperatively, absent femoral, and distal pulses were noted, and thromboembolectomy was performed with good outcome. We believe that our study makes a significant contribution to the literature because it raises awareness of aortic injury and rupture in pediatric patients with multi-organ trauma following motor vehicle accidents. A high index of suspicion and early intervention are essential in improving outcomes.

Favorable response to carbamazepine therapy in genetically proven myoclonus-dystonia child

BackgroundMyoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE).Case presentationWe here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up.ConclusionsOur patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.

Case report of a novel homozygous variant in a Saudi patient with alpha mannosidosis

Background: Alpha-mannosidosis [Online Mendelian Inheritance in Man (OMIM): 248500] is an autosomal recessive disorder due to a deficiency of the lysosomal enzyme alpha-mannosidase. It is an ultra-orphan disease. In this paper, we report a case of alpha-mannosidosis in a Saudi boy of consanguineous parents, who was referred to our hospital to be worked up for possible mucopolysaccharidosis. Case Presentation: The patient was presented with dysmorphic features, global developmental delay, hearing defect, and recurrent respiratory tract infections. On examination, he had short stature, a short neck, cataracts, hearing impairment, chest deformity, hepatomegaly, umbilical hernia, right inguinal hernia, and two Mongolian spots in the back. He had normal peripheral blood smear: urinary oligosaccharide and dry blood spot for mucopolysaccharide enzyme assay founded to be negative. Definitive diagnosis was performed by directly sequencing the MAN2B1 gene of the peripheral blood leukocytes. It showed a homozygous variant c.1065delC; p.Ala356fs*7 (NM_001173498.1) as likely pathogenic. Conclusion: We report a novel variant mutation in MAN2B1 gene mutation. Also, to the best of authors' knowledge, this is the first reported case of alpha-mannosidosis in a Saudi patient.

SUN-LB2 Undescended Testicle and Short Stature as Manifestation of Pituitary Stalk Interruption Syndrome a Report From Saudi Arabia

BackgroundPituitary stalk interruption syndrome (PSIS) is a congenital disease with isolated growth hormone deficiency or multiple anterior pituitary hormone deficiencies. Here, the authors report a case of PSIS from Saudi Arabia.Clinical CaseA 16 year old Saudi boy presented to the endocrine clinic with short stature and undescended testis, status post bilateral orchidopexy. He was delivered by caesarean section because of breech presentation and birth asphyxia. Investigation revealed underdeveloped secondary sexual characteristics with decreased facial and pubic hair growth. The patient height was 134 cm whereas the bone age was 9 - 11 years. Pelvis examination showed a scrotum with bilateral 1 mL testes and the stretch penile length was 3 cm.The patient laboratory investigations showed hemoglobin level of 13 g/dL, serum sodium 140 mmol/L, serum potassium 4.1 mmol/L, serum chloride 102 mmol/L, calcium 9.1 mg/dL, random blood sugar 110 mg/dL and albumin 3.8 mg/dL. A pituitary hormone profile showed hypopituitarism with thyroid, and adrenal sparing. The patient free T4 was 17.3 pmol/L (9-25 pmol/L) and synacthen test revealed a morning baseline cortisol level of 6.5 µg/dL (normal = 4.3-22.4 ug/dL) with adrenocorticotrophic hormone of 9.8 pmol/L (1.1 - 13.2 pmol/L). Insulin-like growth factor 1 level 50 ng/dL (normal = 193.0 - 731.0 ug/L), follicle-stimulating hormone 0.35 µIU/mL (normal, 0.0-10.0), and leutinizing hormone 0.4 µIU/mL (normal = 1.2-7.8). The patient’s morning testosterone level showed 8 ng/dL (normal = 280-800 ng/dL) and prolactin 116 mIU/L (normal = 86 - 324 mIU/L). There were no symptom suggestive of posterior pituitary involvement like polyuria and polydipsia as urine and serum osmolality. The MRI examination showed no pituitary gland identified in the sella turcica and no clear pituitary stalk. A T1 hyperintense focus with post-contrast enhancement was identified posterior to the optic chiasma representing an ectopic posterior pituitary gland. The growth hormone and testosterone therapy were added to medical therapy of the patients and no thyroid or hydrocortisone replacement therapy was given. Conclusion: Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.

A de novo variant of CHD8 in a patient with autism spectrum disorder.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, usually diagnosed in early childhood, that are characterized by adaptive deficits in social interaction, communication skills, and restricted or stereotyped repetitive patterns of behavior. There had been limited success to define ASD subtypes on the behavioral basis. Genetically categorized ASD subtypes may provide basis to determine the course, prognosis, and individualized mechanism based treatment. Mutations in chromodomain helicase DNA-binding protein 8 (CHD8) gene, have been associated with autism, macrocephaly, speech delay, distinct facial features, sleep and gastrointestinal disturbances. There are few cases in the literature reporting de novo mutations of CHD8 exhibiting sporadic ASD. Here we describe a Saudi boy with developmental delay, intellectual disability, macrocephaly, craniofacial abnormalities, speech delay, but without any history of seizures, gastrointestinal problems or sleep disturbance. Whole exome sequencing for parent-child trio revealed a de novo heterozygous loss-of-function mutation (c.4984C>T, p.Arg1662Ter) in CHD8 gene. Our findings elaborate the genotype-phenotype correlation and confirm that the CHD8 disruptions represent a clinical ASD subtype and further highlight the significance of implementing genomic medicine in clinical practice for an early intervention and necessary support for the families.

Unilateral pachydermodactyly in a Saudi boy: A rare presentation

Pachydermodactyly (PDD) is a rare, acquired idiopathic form of digital fibromatosis. PDD typically presents as asymptomatic swelling of the second to fourth proximal interphalangeal joints bilaterally in young males. Here, we present an acquired unilateral PDD in a Saudi boy with emphasis on the clinical, radiological, and histopathological features. In conclusion, PDD is a benign disease; a prompt recognition would prevent irrelevant workup and reassure patients.

Metoclopramide-Induced Extrapyramidal Side Effects are Augmented by Domperidone

Metoclopramide is perhaps one of the most common causes of drug-induced movement disorders. It is indicated in several conditions such as nausea, vomiting, diabetic gastroparesis, small bowel intubation, and gastroesophageal reflux. We report a case of a 15-month-old Saudi boy who was first treated for sudden and persistent nausea and vomiting, accompanied by high-grade fever 39.9°C. The physician started treating him with domperidone (Motilium 1 mg/mL oral suspension) 0.25 mg/kg immediate (stat) dose and, hence, he received a total stat dose of 2.5 mg. He was also prescribed paracetamol suppositories for fever at a dose of 15 mg/kg. Later on, another pediatrician decided to administer a stat dose of metoclopramide at approximately 6 p.m. and he received only a single dose of 1 mg metoclopramide I.V. (Primperan), which stopped the nausea and vomiting instantly. The baby was brought back to the same government hospital at 12 a.m., presenting typical extrapyramidal symptoms (EPS). He was treated successfully with only diazepam.

Bi-rooted primary maxillary canines: a case report

BackgroundAnomalies in primary teeth are comparatively fewer than in the permanent teeth. The presence of a primary canine with two roots is very rare. An unusual anomaly like this may lead to problems during extraction or exfoliation. Emphasis on the importance of anomalies is required for proper diagnosis and to facilitate a better treatment outcome.Case presentationThe present case report describes a case of a bilateral bi-rooted primary maxillary canines diagnosed during a radiographic examination in a 9-year-old Saudi boy. To the best of our knowledge, this is the first case of bi-rooted primary maxillary canine reported from the region of Saudi Arabia.ConclusionThis case report aims to increase awareness of the morphological alterations in primary canines and to emphasize the importance of diagnosis and radiographic examination using different angles. Clinicians should consider all the possible tooth variations during routine intra-oral and radiographic examinations to facilitate a better treatment outcome and to avoid unwanted complications.

An anti-n-methyl-d-aspartate receptor antibody syndrome-like presentation and negative result of testing for autoantibodies in a Saudi boy

An anti-n-methyl-d-aspartate receptor antibody syndrome-like presentation and negative result of testing for autoantibodies in a Saudi boy

Rubinstein-Taybi syndrome in a Saudi boy with distinct features and variants in both the CREBBP and EP300 genes: a case report

BackgroundRubinstein-Taybi syndrome (RSTS) Type 1 (OMIM 180849) is characterized by three main features: intellectual disability; broad and frequently angulated thumbs and halluces; and characteristic facial dysmorphism.Case presentationWe report on a Saudi boy with RSTS Type 1 and the following distinct features: a midline notch of the upper lip, a bifid tip of the tongue, a midline groove of the lower lip, plump fingers with broad / flat fingertips, and brachydactyly. The child was found to be heterozygous in the CREBBP gene for a sequence variant designated c.4963del, which is predicted to result in premature protein termination p.Leu1655Cysfs*89. The child and his father were also found to be heterozygous in the EP300 gene for a sequence variant designated c.586A > G, which is predicted to result in the amino-acid substitution p.Ile196Val.ConclusionOur report expands the clinical spectrum of RSTS to include several distinct facial and limb features. The variant of the CREBBP gene is known to be causative of RSTS Type 1. The variant in the EP300 gene is benign since the father carried the same variant and exhibited no abnormalities. However, functional studies are required to investigate if this benign EP300 variant influences the phenotype in the presence of disease-causing CREBBP gene mutations.