Sanjad-Sakati Syndrome Research Articles

Measurement of the Neutrophils Count and Oxidative Burst in Neutrophils of Patients with Sanjad Sakati Syndrome.

Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these patients may affect the nature and function of the immune system. Thus, in this study, cell count and phagocytotic function of neutrophils were evaluated which may be influenced by changes in the hormonal rate and growth factors. In this study, the neutrophil count value and the oxidative burst were evaluated in six patients diagnosed with SSS and six healthy individuals. There was a significant reduction in the neutrophil count observed in SSS patients compared to healthy controls (37.41±7.93 percent vs. 66.5±6.8 percent). However, there was no significant difference in neutrophil oxidative index between patients with SSS and control subjects (172.33±55.08 vs. 217.00±77.38). We concluded that in patients with SSS, the phagocytic activity of neutrophils was not affected by hormonal changes, while the number of neutrophils and neutrophil-to-lymphocyte ratio (NLR) index were decreased.

RECURRENT PSEUDO-OBSTRUCTION OF THE LARGE BOWEL ASSOCIATED WITH SANJAD-SAKATI SYNDROME: A CASE REPORT

Sanjad-Sakati Syndrome, also referred to as Hypoparathyroidism-Retardation-Dysmorphism Syndrome or Middle East Syndrome, was first reported in Saudi Arabia in 1988 and later in a definitive report by (Sanjad et al.) in 1991. It is a rare autosomal recessive condition reported almost exclusively in the Arab population. The condition is characterized by an extensive array of symptoms, including congenital hypoparathyroidism, severe growth and developmental retardation both intrauterine and post-natal, low Intelligence, seizures, and distinctive facial characteristics. We present an incidence of this disease characterized by repeated pseudo-obstruction. Electrolyte and metabolic disturbances, which are the cause of pseudo-obstruction of the intestine in this child, must be evaluated in order to avoid unnecessary surgical intervention, which may prove to be life threatening.

Sanjad-Sakati Syndrome in Al Najaf Governorate

Sanjad-Sakati syndrome is an inherited autosomal recessive disorder that presents primarily in the Arab countries, with its real prevalence not well established. It is a combination of specific facial dysmorphology, failure to thrive, hypoparathyroidism, and variable mental disability which is an unfortunately incurable disease with fatal outcomes.

Homozygous TBCE Gene Mutation c.155-166del in a Libyan Patient with Sanjad-Sakati Syndrome: Same Gene Mutation Responsible in All Arab Ethnic Patients.

Sanjad-Sakati syndrome (SSS) (Online Mendelian Inheritance in Man 241410) is a rare autosomal recessive disorder also known as hypoparathyroidism-retardation-dysmorphism syndrome. It is characterized by congenital hypoparathyroidism, growth retardation, typical facial features, and variable developmental delay. SSS is caused due to mutations of the tubulin-specific chaperone E ( TBCE ) gene. In this article, we reported the first Libyan child of first parental consanguinity with SSS and whole exome sequencing results identified the homozygous missense variant c.155-166del and it encodes p.(Ser52-Gly55del) (chr1:235564867) located in the TBCE gene , chromosome 1q42.3. In addition, the patient was also diagnosed with congenital hypothyroidism and presented with acquired bilateral cataract in the first year of life. Most likely, all Arab patients with SSS syndrome have the same TBCE gene mutation.

IDF21-0574 Type 1 Diabetes onset and COVID-19 infection in a child with Sanjad Sakati Syndrome: a case from Kuwait

Background: Sanjad Sakati Syndrome (SSS) is an autosomal recessive multisystem disorder characterized by congenital hypoparathyroidism, prenatal and postnatal growth and mental delay, dysmorphic features, and hypocalcemia seizures. It has not been linked with autoimmune disorders such as Type 1 Diabetes (T1D). Viral infections may play a role in triggering the development of T1D. Contracting SARS-CoV-2 virus may induce an autoimmune response by damaging the pancreatic β cells and accelerate the onset of T1D. To the best of our knowledge, no case studies of SSS has been reported to develop T1D were reported. Aim: To present a child with SSS who was newly diagnosed with T1D and SARS-CoV-2 infection (COVID-19). Method: Data on the patient were extracted from the Childhood Onset Diabetes electronic Registry (CODeR) in Kuwait. Results: The child was diagnosed early in life with SSS by tubulin-specific chaperone E (TBCE) gene mutation. The child is under multidisciplinary care and managed by alphacalcidol treatment. In May 2021, she presented with a history of fever, cough, polyuria, polydipsia, and poor appetite which lasted for 6 days. On investigations, random blood sugar level was 22 mmol/l and HbA1c level was 10%. There was no evidence of diabetic ketoacidosis. Autoantibodies to glutamic acid decarboxylase (GAD) and thyroperoxidase antibodies (TPO) were positive, with normal thyroid function results. Serum insulin and c-peptide levels were low (0.93 miu/ml, 28 pmol/l respectively). Thus, T1D diagnosis was made, and insulin therapy was started. No family history of diabetes was reported. On admission, the child tested positive for SARS-CoV-2 PCR and had positive contacts with family members with COVID-19 infection. As per WHO COVID-19 infection severity criteria, the child’s condition was classified as mild. She was discharged home with no short-term sequelae of COVID-19 infection; diabetes and dietary education was provided. Discussion: To the best of our knowledge, this is the first case reported in literature of a patient with SSS who presented with T1D onset along with COVID-19 infection. Viral infections such as SARS-CoV-2 virus may trigger the development of autoimmune diseases such as T1D. Exploring the relationship between COVID-19 infection and T1D onset is needed for better understand the effect of COVID-19 infection and outcome on pediatric patients with comorbidities. Further explorations are also needed to study the relationship of SSS and autoimmune disorders as well; to fully appreciate the impact on such patients.

Oral Facial Manifestations of Sanjad-Sakati Syndrome: A Literature Review.

Aim: To perform a comprehensive review of orofacial manifestations of Sanjad–Sakati syndrome (SSS). Methods: A comprehensive electronic literature search was performed using PubMed, Scopus and Cochrane library databases. The search keywords included were “Sanjad–Sakati syndrome (SSS)”, “dental manifestations”, “dental management”, “oral health”, “dental care for patients with SSS”, “dental health of people with SSS”, “caries”, and “oral hygiene”. The inclusion criteria were papers published only in English, papers published by August 2021, and papers discussing orofacial manifestations of SSS and language. Results: The search of the databases retrieved eleven case reports and three case series studies. Overall, 56 cases (11 case reports and 3 case series studies) were reported on Sanjad–Sakati syndrome in the published literature. The majority of the reports are from the Middle Eastern region. Conclusions: The reported orofacial manifestations of SSS include beaked nose, depressed nasal bridge, enamel hypoplasia, hypodontia, low-set ears, posteriorly rotated ears, deep-set eyes, microcephaly, microdontia, micrognathia, prominent forehead, retrognathia, and thin lips. The review paper also establishes the importance of the dental under general anesthesia in SSS individuals.

Sanjad Sakati syndrome and sleep-disordered breathing: an undisclosed association.

Sanjad Sakati syndrome (SSS) is a rare autosomal recessive genetic disorder caused by mutation in TBCE (tubulin folding cofactor E) gene. Reported cases were almost exclusively of Middle-Eastern and Arabian children of consanguineous parents. We report the clinical manifestations, outcome, and an observed new association of sleep-disordered breathing (SDB) among children with Sanjad Sakati syndrome. Clinical and routine laboratory data of SSS cases attending Sultan Qaboos University Hospital, Oman, were collected from the electronic patient records or through direct clinic interviews. In-lab polysomnography (PSG) and echocardiography were carried out for all the cases. SDB diagnosis was based on the guidelines of the American Academy of Sleep Medicine. Of 12 patients with SSS, 5 males (42%), all of them (100%) had obstructive sleep apnea (OSA) and 4 of them(33%) had additional significant central apnea and sleep-related hypoventilation. Eight patients (67%) had severe SDB with mean apnea-hypopnea index (AHI) of 26.5 events/h. Age at time of diagnosis with SDB ranged from 2 to 17years with mean of 8.9 [Formula: see text] Two patients had severe pulmonary hypertension as a complication of severe SDB and died from type 2 respiratory failure. Sleep-disordered breathing is prevalent among children with SSS, especially OSA. This is the first study to report SDB in a large cohort of patients with this extremely rare syndrome. The study results encourage the importance of screening affected patients with SSS for sleep-disordered breathing early before developing severe morbidities such as pulmonary hypertension that further compromise their quality of life.

Airway Challenges in Sanjad-Sakati Syndrome (SSS): A Case Report and Review of Literature

Sanjad-Sakati Syndrome (SSS) is a rare syndrome, discovered in Saudi Arabia in 1988. This syndrome is characterized by congenital hypoparathyroidism, severe growth retardation, dysmorphic features, mild to severe mental retardation as well as recurrent chest infections. We presented an eight-year-girl with SSS, with severe growth retardation, mental retardation, resolution of recent chest infection together with a history of bronchial asthma, dysmorphic features, limited mouth opening, micrognathia as well as high susceptibility to difficult intubation. The objective of this case report is to present the successful anaesthetic management of a rare genetic endocrinal syndrome.

Correcting hypophosphataemia in a paediatric patient with Sanjad–Sakati syndrome through a single oral dose of potassium phosphate intravenous solution

Sanjad–Sakati syndrome is an autosomal recessive disorder that is quite common in Kuwait. Among a wide range of complications in Sanjad–Sakati syndrome patients is the vulnerability to infections and subsequent hypophosphataemia. Hypophosphataemia is a metabolic alteration that contributes to numerous consequences such as cardiac arrhythmia. Therefore, if hypophosphataemia is left unresolved, it may culminate in death. A 20-month-old boy of 2.5 kg body weight diagnosed with Sanjad–Sakati syndrome was initially admitted to the paediatric intensive care unit after recovering from COVID-19, and then shifted to the general ward. He was diagnosed with recurrent pneumonia and urinary tract infection. After 9 days, the patient showed severe hypophosphataemia with serum phosphate concentration reaching 0.33 mmol/L. Despite the availability of potassium phosphate intravenous solution, it was difficult to administer potassium phosphate intravenously because of the small body size and low body weight of the patient. Therefore, 0.6 mL potassium phosphate containing 2.4 mEq of potassium and 5.3 mEq of phosphate was administered through a nasogastric tube. The patient showed rapid response after a single dose through the nasogastric tube. Such an intervention in Sanjad–Sakati syndrome patients shows possible advantages of shifting drug administration from intravenous to oral route that includes a convenient route of administration, whether in the intensive care unit or in the general ward. Moreover, shifting drug administration from the intravenous to oral route overcomes the risk of cannula-induced infection and reduces nurses’ workload.

Endocrinological Manifestations of Sanjad-Sakati Syndrome.

Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, is a very rare genetic disorder with an autosomal recessive mode of inheritance, mostly seen in children of Middle Eastern origin. Hypoparathyroidism remains the most characteristic endocrinological feature of SSS; but not the only one. This review outlines and elucidates other endocrinological manifestations that may be seen with this syndrome.

Clinical features and tubulin folding cofactor E gene analysis in Iranian patients with Sanjad‐Sakati syndrome

ObjectivePermanent hypoparathyroidism can be presented as part of genetic disorders such as Sanjad–Sakati syndrome (also known as hypoparathyroidism—intellectual disability‐dysmorphism), which is a rare autosomal recessive disorder. Our aim was to confirm the diagnosis of a group of patients with dysmorphism, poor growth, and hypoparathyroidism clinically labeled as Sanjad–Sakati syndrome and to identify for the first time the genetic variations on Iranian patients with the same ethnic origin. MethodsIn this study, 29 cases from 23 unrelated Arab kindreds with permanent hypoparathyroidism and dysmorphism indicating Sanjad‐Sakati syndrome were enrolled for 10 years in the southwest of Iran. The mutational analysis by direct sequencing of the tubulin folding cofactor E gene was performed for the patients and their families, as well as their fetuses using genomic DNA. ResultsTwenty‐eight out of 29 cases had parental consanguinity. Twenty‐seven cases presented with hypocalcemia seizure and two were referred because of poor weight gain and were found to have asymptomatic hypocalcemia. The dysmorphic features, hypocalcemia in the setting of low to normal parathyroid hormone levels and high phosphorus led to the diagnosis of these cases. Sequencing analysis of the tubulin folding cofactor E gene revealed a homozygous 12‐bp deletion (c.155–166del) for all patients. Following that, prenatal diagnosis was performed for eight families, and two fetuses with a homozygous 12‐bp deletion were identified. ConclusionThese results make it much easier and faster to diagnose this syndrome from other similar dysmorphisms and also help to detect carriers, as well as prenatal diagnosis of Sanjad‐Sakati syndrome in high‐risk families in this population.

Neurological Manifestations of Sanjad–Sakati Syndrome: New Three Reported Cases from Tunisia

AbstractSanjad–Sakati syndrome (SSS), or hypoparathyroidism–mental retardation dysmorphism syndrome, is a rare autosomal recessive congenital disorder characterized by congenital hypoparathyroidism, growth and neurodevelopmental delay, acute symptomatic seizures due to hypocalcemia, and dysmorphic features. The syndrome is underdiagnosed, and neurological manifestations are not previously described. We report three Tunisian patients with SSS revealed by acute symptomatic hypocalcemic epileptic seizures. Despite the well-controlled seizures, patients tend to continue having poor growth and neurological outcome. The diagnosis of SSS allowed for proper treatment of the patients, prevented associated comorbidities, and provided genetic counseling to their families.

SUN-518 Sanjad Sakati Syndrome - A Rare Cause Of Congenital Hypoparathyroidism And Severe Short Stature - A Case Report

BACKGROUND: Sanjad-Sakati Syndrome (SSS) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism, dysmorphic facial features, short stature, and developmental delays (1). SSS has been reported primarily in individuals of Middle Eastern ancestry. Children are born with features of intrauterine growth restriction and demonstrate poor postnatal growth. Acquired hypothyroidism has been reported. There are no previous reports of osteopenia in older children with SSS. CLINICAL CASE: A 17-year-old male Syrian refugee with a history of clinical diagnosis of SSS presented to our endocrine clinic. He is the product of consanguineous marriage born at 40 weeks gestation and weighing 2 kg at birth. He was admitted at Syrian hospital at age 2 weeks for seizures and found to have hypocalcemia and undetectable parathyroid hormone level. He began calcium and vitamin D replacement. He had 4-5 seizures in the first few years of life. Patient began Alfacalcidol around age 5 and his symptoms improved. Upon referral to our institution at age 17, he had classic features of SSS and next generation sequencing confirmed TBCE mutation. Weight was 13.6 kg (-24.8 SD weight for age). Height was 104 cm (-8.86 SD height for age). Bone age was 17 years. He was Tanner stage 3 for pubic hair with normal adult phallus. Testicular volume was 6-8 cc bilaterally. LH was 6.8 miIU/mL, FSH was 19.3 miIU/mL, and total testosterone was 726 ng/dL. Ultrasounds showed bilateral nephrocalcinosis and testicular microlithiasis. He had significant cervical and thoracolumbar scoliosis due to muscle atrophy leading to contractures. MRI revealed basal ganglia calcifications. He had a steady neurologic decline including poor balance and strength, pain with ambulation, and now requires wheelchair assistance. He had no history of fractures, however, due to his symptoms DXA was obtained. Left Distal Femur BMD Z-scores were R1 -4.5, R2 -6.8, R3 -4.7. Right Distal Femur BMD Z-scores were R1 -4.4, R2 -6.4, R3 -4.7. There was no solution for adjusting for height for distal femur results. MRI spine did show increased marrow fat. CONCLUSIONS: We conclude that adolescents with SSS may demonstrate osteopenia, however severe scoliosis and short stature make positioning for DXA and interpretation of DXA challenging. Osteopenia may be due to inherent risk factors of osteopenia such as poor mobility, poor nutrition from feeding issues, or nutritional deficiencies. Hypogonadism could also contribute to osteopenia; however, in our patient, normal testosterone levels were observed at presentation even in the setting of small testicular size and testicular microlithiasis. REFERENCES: 1. Arabi, W.A., A.A. Basheer, M.A. Abdullah. Sanjad-Sakati Syndrome in Sudanese children. Sudan J Paediatr, 2011. 11(1): p.42-7.

Additional Tunisian patients with Sanjad–Sakati syndrome: A review toward a consensus on diagnostic criteria

Background and objectivesSanjad–Sakati syndrome (SSS; OMIM 241410) is a rare autosomal recessive disorder found almost exclusively in people of Arab origin. It is characterized by congenital hypoparathyroidism, severe prenatal and postnatal growth retardation, and distinct facial dysmorphism. The molecular pathology of this syndrome was shown to be due to a mutation in the tubulin-specific chaperone E (TBCE) gene in chromosomal area 1q42-q43. We aimed to detect and confirm the common mutation responsible for SSS in Tunisian patients and review the literature in order to create a set of clinical diagnostic criteria that might provide appropriate indications for molecular testing. MethodsThree Tunisian patients with clinical feature of SSS were examined via direct Sanger sequencing of exon 3 of the TBCE gene. ResultsMutation analysis of the TBCE gene revealed the common 12-bp (155-166del) deletion in three new patients, thus raising the number of reported SSS patients to 73. Reviewing the literature, we suggest a scoring system that assigns one point each for major criteria and one half point for minor criteria. Interpretation and conclusionsSSS is an autosomal recessive disorder found in the Middle Eastern population with an estimated incidence of 1 per 40,000–100,000 live births in Saudi Arabia. Reviewing the literature on both its clinical and biochemical characteristics, we suggest for the first time, based on defined major and minor SSS criteria, a clinical scoring system for the diagnosis of SSS. On the one hand, an established scoring system will provide appropriate indications for molecular testing and, on the other hand, reviewed data on SSS will help delineate the phenotype and draw a distinction between differential diagnoses.

Sanjad–Sakati Syndrome: An Anesthetic Challenge

Due to scarce data regarding “Middle Eastern Syndrome” or the Sanjad–Sakati syndrome, this case report aims to elaborate the significance of this rare autosomal recessive syndrome and the considerations to provide anesthesia to such patients. The patient discussed in this report is a diagnosed case of Sanjad– Sakati syndrome, indicated for surgical insertion of gastrostomy tube by laparotomy. The anesthetic concerns encountered included a difficult airway anatomy due to facial dysmorphic features and short stature, along with increased sensitivity to muscle relaxants. The case was further complicated by the presence of chest infection and electrolyte imbalance, particularly hypocalcemia, with the risk of seizures, cardiovascular collapse, and arrhythmias. A thorough preoperative assessment and multidisciplinary approach, including correction of electrolytes and optimization of the chest condition, followed by a cautious and vigilant intraoperative anesthetic management and close postoperative monitoring led to a smooth recovery and positive outcome with the avoidance of any morbidity or mortality.

Clinical features and tubulin folding cofactor E gene analysis in Iranian patients with Sanjad–Sakati syndrome

ObjectivePermanent hypoparathyroidism can be presented as part of genetic disorders such as Sanjad–Sakati syndrome (also known as hypoparathyroidism—intellectual disability-dysmorphism), which is a rare autosomal recessive disorder. Our aim was to confirm the diagnosis of a group of patients with dysmorphism, poor growth, and hypoparathyroidism clinically labeled as Sanjad–Sakati syndrome and to identify for the first time the genetic variations on Iranian patients with the same ethnic origin. MethodsIn this study, 29 cases from 23 unrelated Arab kindreds with permanent hypoparathyroidism and dysmorphism indicating Sanjad-Sakati syndrome were enrolled for 10 years in the southwest of Iran. The mutational analysis by direct sequencing of the tubulin folding cofactor E gene was performed for the patients and their families, as well as their fetuses using genomic DNA. ResultsTwenty-eight out of 29 cases had parental consanguinity. Twenty-seven cases presented with hypocalcemia seizure and two were referred because of poor weight gain and were found to have asymptomatic hypocalcemia. The dysmorphic features, hypocalcemia in the setting of low to normal parathyroid hormone levels and high phosphorus led to the diagnosis of these cases. Sequencing analysis of the tubulin folding cofactor E gene revealed a homozygous 12-bp deletion (c.155–166del) for all patients. Following that, prenatal diagnosis was performed for eight families, and two fetuses with a homozygous 12-bp deletion were identified. ConclusionThese results make it much easier and faster to diagnose this syndrome from other similar dysmorphisms and also help to detect carriers, as well as prenatal diagnosis of Sanjad-Sakati syndrome in high-risk families in this population.

Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series.

BackgroundHypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism.MethodsWe describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements.ResultsThree infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation.ConclusionIntercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis.

Sanjad-Sakati syndrome: Beyond the Middle-East

Sanjad-Sakati syndrome (OMIM 241410), also known as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, is a rare autosomal recessive syndrome of congenital hypoparathyroidism, mental retardation, and facial dysmorphism, reported almost exclusively in the Middle-Eastern children of consanguineous parents. Here, we present a 20-year-old male child from India presenting with childhood-onset, recurrent generalized seizures, which were poorly controlled with multiple antiepileptics. Along with intrauterine growth retardation, the patient had short stature and typical facial dysmorphism. Investigations revealed extensive intracranial calcifications, with hypoparathyroidism and severe hypocalcemia. This is only the third reported patient of HRD phenotype in a non-Arab patient and the first to present with multifocal dystonia. Thus, it is important to keep in mind untreated hypocalcemia in a patient of refractory seizures, with HRD possibly being no longer an exclusively Middle-Eastern disease.

Sanjad-Sakati syndrome in a Tunisian child

Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism with growth and mental retardation associated with seizures and a characteristic physiognomy. SSS molecular pathology has been shown to be due to mutations in the TBCE gene on chromosome 1q42-q43. All affected patients of Arab origin are homozygous for a 12-bp (155-166del) deletion in exon 3 of this gene. We report on a Tunisian child with SSS who was homozygous for the 155-166del mutation. Our findings provide additional support of the common (155-166del) deletion founder effect in exon 3 of the TBCE gene in Arab patients. It is very likely that this mutation originated in the Middle East and was introduced in Tunisia by the Banu Hilal invaders.

New Assay of Detecting Common Mutation Causing Sanjad-Sakati Syndrome Using Real-Time Fluorescence PCR and Melting Curve Analysis

Sanjad-Sakati Syndrome (SSS) is an autosomal recessive disorder reported mainly in Middle Eastern populations.The mutation c.155_166del in exon 3 of theTBCE gene is the most common cause of SSS in the population.Each double stranded DNA product has a specific melting temperature (Tm) at which50% of the DNA is single stranded. By using melting curve analysis we present a new assay for rapid genotyping of SSS (l ess than one hour) to be used in prenatal and preimplantation genetic diagnosis (PGD) settings.