Glutaric Aciduria Type Research Articles

Preimplantation genetic testing for inborn errors of metabolism: observations from a reproductive genetic laboratory in China.

In this study, we aimed to apply preimplantation genetic testing for monogenic disorders (PGT-M) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to block the transmission of inborn errors of metabolism (IEMs). After the disease-causing variants were identified through genetic testing, four carrier couples having children affected with IEMs, including methylmalonic aciduria, glutaric acidemia type 1, beta-ketothiolase deficiency, and ornithine transcarbamylase deficiency, sought PGT-M. A series of PGT procedures involving intracytoplasmic sperm injection, blastocyst culture, biopsy of trophectoderm cells, and next-generation sequencing (NGS)-based MARSALA, was performed to provide comprehensive chromosome screening and variant gene analysis. Finally, embryos were selected for transfer, and prenatal diagnosis was conducted to confirm the PGT-M results. All four carrier couples obtained transferrable embryos after PGT. The results of the prenatal diagnosis were consistent with the PGT results, and all couples gave birth to healthy babies free of IEMs. The results of this study confirm that NGS-based MARSALA is an effective approach for families with IEMs to prevent the subsequent transmission of pathological genetic variants to the next generation.

Gluteric aciduria ( type-I) Presenting as Bilateral Subdural Hygroma- A Case Report with Literature Review

Glutaric aciduria type 1 (GA-1) is an autosomal recessive rare neurometabolic disorder caused by absent or deficient activity of glutaryl- CoA dehydrogenase. Patient with gluteric aciduria are more likely to develop collection in the subdural space secondary to cerebral atrophy and expansion of CSF spaces. A 1 year and 10 months toddler presented with increased head circumference since birth and generalized seizure for last few days. Neuroimaging showed bilateral subdural collection of CSF intensity. Bilateral subdural peritoneal shunt was inserted. With early diagnosis and adequate treatment , the majority of children with gluteric aciduria type-I are able to live normal. However treatment for gluteric aciduria type-I must be continued for life to avoid lifethreatening complications Bang. J Neurosurgery 2024; 13(2): 162-164

Common Organic Acidemias in a Tertiary Hospital in Egypt

Abstract Background Organic acidemias (OAs) are a heritable group of heterogeneous metabolic disorders characterized by the accumulation of organic acids in body fluids and tissues. They are rare disorders and infrequently reported worldwide. Methylmalonic acidemia (MMA), propionic acidemia (PA), isovaleric acidemia (IVA), 3-methylglutaconic aciduria (3-MGA), and glutaric acidemia type 1(GA1), are considered the more common OAs, their prevalence is higher in Arab populations due to the high consanguinity rate. Aim This study aimed to: • Evaluate the spectrum of common organic acidemias among pediatric patients who followed up at the metabolic clinic of a tertiary hospital in Egypt. • Present different clinical and biochemical characterizations and the time of onset of these disorders, so that helps in raising the high index of suspicion among pediatricians and health care practitioners to make an early diagnosis. Method We conducted a descriptive retrospective study by reviewing the medical records of pediatric aged group patients diagnosed with common forms of OAs, followed up in Metabolic Clinic, Ain Shams University Hospitals, Egypt, over a 4-year period, between January 2017 and January 2021. All patients were investigated by metabolic work up, including the acylcarnitine profile and urinary organic acid analysis. Results A total of 76 patients with common OAs were included in the study. There were (56.6%) males and (43.4%) females. Most patients presented after the first year of life (58.7%); whereas the median age at diagnosis was 15 months. GA-1 was the most frequent disorder (39.5%), followed by MMA (36.8%). There were relatively high rates of consanguinity (80%) and affected siblings (23%). The most frequent presenting symptoms were developmental delay (69.3%), poor feeding (65.7%), and vomiting (50.7%). The main observed complications among studied patients were delayed motor development (67.1%), delayed speech (22.4%) and faltering growth (15.8%). Regarding the disease course and patientś outcome; 55.3% of patients exhibited regressive course, whereas 84.2% of patients were alive and well. Conclusion GA-1 is the commonest organic acidemias in Egypt and is more evident due to high rate of consanguinity. This urges the need to enhance awareness among pediatricians, primary healthcare providers and devise a governmental newborn screening program for the early detection and prevention of such disorders.

Intrathecal baclofen therapy as treatment for spasticity and dystonia: Review of cases in a pediatric palliative care unit

IntroductionPatients managed in the Pediatric Palliative Care Integral Unit (PPCIU) have serious neurological conditions that involve significant damage at central nervous system level. The movement disorder is a very common clinical problem and for the patients where an adequate control of muscle tone is not achieved with usual techniques or drugs, intrathecal baclofen therapy (IBT) should be considered. Materials and methodsDescriptive retrospective study based on the review of clinical records of patients who received IBT being followed by the PPCIU of Madrid Autonomous Region in the timeframe between September 2012 and February 2021. ResultsIBT was implanted in 8 patients affected by infantile cerebral palsy (ICP) with a Gross Motor Function Scale (GMFCS) IV–V, 3 patients was a Pantothenate kinase deficit-associated neurodegeneration (PKAN), 2 had Acquired Brain Damage, and the remaining 3 had, respectively, 2 glutaric aciduria type I (GA-1), and poly-malformative syndrome. In all patients we observed a period of clinical stability after IBT, we call this period “honeymoon”. Two patients died while in the honeymoon period, at 24.9 and 19.6 months from implantation of the pump; the median of duration of the honeymoon period in the remaining 14 was 14.4 months (IQ: 8.3–25.8). ConclusionsIBT was not only used in patients with non-progressive diseases, but also in the group of patients with neurodegenerative or progressive diseases. In all of them, after implantation of the device, we have objectified a period of clinical stability and a better control of muscle tone disorders.

Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1.

Allosteric regulators acting as pharmacological chaperones hold promise for innovative therapeutics since they target noncatalytic sites and stabilize the folded protein without competing with the natural substrate, resulting in a net gain of function. Exogenous allosteric regulators are typically more selective than active site inhibitors and can be more potent than competitive inhibitors when the natural substrate levels are high. To identify novel structure-targeted allosteric regulators (STARs) that bind to and stabilize the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH), the computational site-directed enzyme enhancement therapy (SEE-Tx) technology was applied. SEE-Tx is an innovative drug discovery platform with the potential to identify drugs for treating protein misfolding disorders, such as glutaric acidemia type 1 (GA1) disease. Putative allosteric regulators were discovered using structure- and ligand-based virtual screening methods and validated using orthogonal biophysical and biochemical assays. The computational approach presented here could be used to discover allosteric regulators of other protein misfolding disorders.

Diagnostic challenges and outcome of fatty acid oxidation defects in a tertiary care center in Lebanon

BackgroundFatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East.MethodsA retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype–phenotype correlation was also performed, when available.ResultsSeven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in the SLC22A5 gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis.ConclusionsOur experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians’ awareness and systematic neonatal screening are key for diagnosis. Larger genotype–phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome.

Enhanced differentiation between 3-hydroxyglutaric and 2-hydroxyglutaric acids facilitates diagnostic testing for glutaric aciduria type 1.

Glutaric aciduria type 1 (GA1) is an inherited neurometabolic disorder, in which deficiency of glutaryl-CoA dehydrogenase leads to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3-HG). Some low excretors may exhibit only slight elevation of urinary 3-HG, with normal urinary GA, yet are at significant risk of severe clinical disease. Accurate quantitation of urinary 3-HG is crucial in diagnostic workup for GA1, but in this context, current gas chromatography-mass spectrometry (GC-MS) methods have inherent analytical challenges. Co-elution and spectral similarities of the 3-HG and 2-HG structural isomers can cause difficulties in quantitation of slightly elevated 3-HG. Our laboratory recently acquired a gas chromatography system coupled to a triple quadrupole mass spectrometer (GC-MS/MS), and we took advantage of its increased sensitivity and specificity to improve our existing GC-MS method. A stable isotope dilution process is used, with sample treatment consisting of a double liquid-liquid extraction followed by a trimethylsilyl derivatization. The transitions m/z 349 → 333 for 3-HG and m/z 349 → 321 for 2-HG were selected to differentiate these two isobaric molecules based on their characteristic fragments, thus minimizing interferences despite co-elution. Method validation demonstrated satisfactory precision and accuracy. Using GC-MS/MS instead of GC-MS allowed us to decrease the required specimen volume, number of sample processing steps, chromatographic run time, and instrument maintenance. This enhanced assay facilitates clinical laboratory testing for GA1, both in confirmatory protocols following positive newborn screening and in diagnostic investigation of patients with suggestive signs or symptoms.

Multiple acyl-Coa dehydrogenase deficiency: an underdiagnosed disorder in adults.

Inherited metabolic diseases, as a first presentation in adults, are an under-recognised condition associated with significant morbidity and mortality. Diagnosis is challenging because of non-specific clinical and biochemical findings, resemblance to common conditions such as neuropsychiatric disorders and the misconception that these disorders predominantly affect paediatric populations. We describe a series of patients with multiple acyl-CoA dehydrogenase deficiency (MADD)/MADD-like disorders to highlight these diagnostic challenges.

Late-onset myopathies.

Late-onset myopathies are defined as muscle diseases that begin after the age of 50 years. Some myopathies present classically in the elderly, whereas others may have a variable age of onset, including late-onset presentation. The purpose of this review is to summarize and comment on the most recent evidence regarding the main diagnosis of late-onset myopathies focusing on genetic causes. Although late-onset myopathies (LOM) are expected to be predominantly acquired myopathies, some common genetic myopathies, such as facioscapulohumeral muscular dystrophy (FSHD), can present late in life, usually with an atypical presentation. In addition, metabolic myopathies, which are classically early-onset diseases, are also diagnoses to be considered, particularly as they may be treatable. Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) has recently been identified as a cause of subacute LOM with a dramatic response to riboflavin supplementation. Inclusion body myositis is the most frequent of all LOM. Myotonic dystrophy type 2, FSHD and oculopharyngeal muscular dystrophy are the most frequent causes of genetic LOM. We summarize the major differential diagnoses and the clinical features on clinical examination that are suggestive of a genetic diagnosis to provide a diagnostic approach.

Cerebral White Matter Alterations Associated With Oligodendrocyte Vulnerability in Organic Acidurias: Insights in Glutaric Aciduria Type I.

The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.

Prenatal Ultrasound and Magnetic Resonance Findings of Glutaric Acidemia Type 1 and Its Challenges in Prenatal Diagnosis.

Glutaric acidemia type 1 (GA1) presents unique challenges in prenatal diagnosis, especially in cases with no family history. This review article aims to review and present the prenatal ultrasound and magnetic resonance findings of GA1 and consolidate key insights into the difficulties associated with GA1 prenatal diagnosis and the neuroimaging features that require careful differentiation during the diagnostic process.

A compound heterozygote case of glutaric aciduria type II in a patient carrying a novel candidate variant in ETFDH gene: A case report and literature review on compound heterozygote cases.

Glutaric aciduria type II (GA2) is a rare genetic disorder inherited in an autosomal recessive manner. Double dosage mutations in GA2 corresponding genes, ETFDH, ETFA, and ETFB, lead to defects in the catabolism of fatty acids, and amino acids lead to broad-spectrum phenotypes, including muscle weakness, developmental delay, and seizures. product of these three genes have crucial role in transferring electrons to the electron transport chain (ETC), but are not directly involve in ETC complexes. Here, by using exome sequencing, the cause of periodic cryptic gastrointestinal complications in a 19-year-old girl was resolved after years of diagnostic odyssey. Protein modeling for the novel variant served as another line of validation for it. Exome Sequencing (ES) identified two variants in ETFDH: ETFDH:c.926T>G and ETFDH:c.1141G>C. These variants are likely contributing to the crisis in this case. To the best of our knowledge at the time of writing this manuscript, variant ETFDH:c.926T>G is reported here for the first time. Clinical manifestations of the case and pathological analysis are in consistent with molecular findings. Protein modeling provided another line of evidence proving the pathogenicity of the novel variant. ETFDH:c.926T>G is reported here for the first time in relation to the causation GA2. Given the milder symptoms in this case, a review of GA2 cases caused by compound heterozygous mutations was conducted, highlighting the range of symptoms observed in these patients, from mild fatigue to more severe outcomes. The results underscore the importance of comprehensive genetic analysis in elucidating the spectrum of clinical presentations in GA2 and guiding personalized treatment strategies.

Role of Botulinum Toxin in Treatment of Secondary Dystonia: A Case Series and Overview of Literature.

Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic conditions which produce varied neurologic as well as systemic manifestations other than dystonia. Chemo-denervation with botulinum toxin has been successfully used for focal or segmental dystonia. However, studies evaluating the effect of BoNT therapy on patients with secondary dystonia are sparse, given the heterogeneity in etiology and presentation. We present a series of patients with secondary dystonia who were managed with botulinum toxin therapy. Patients included in this series had a confirmed neurometabolic cause of dystonia. A total of 14 patients, with ages ranging from 17 to 36 years, with disorders including Wilson's disease, pantothenate kinase-associated neurodegeneration (PKAN), Niemann-Pick disease type C (NPC), glutaric aciduria type 1, Sanfilippo syndrome (Mucopolysaccharidosis Type IIIb), and GM2 gangliosidosis (Sandhoff disease) are presented. Most patients experienced a mild to moderate improvement in treated dystonia with benefits ranging from 6 to 12 weeks, with the median length of the benefits lasting approximately eight weeks, without any significant adverse effects. Although the secondary causes of dystonia are complex and diverse, our presented data and the available reports of the use of botulinum toxin support the conclusion that chemo-denervation plays an important role in symptom alleviation.

Generation of hiPSC lines from four glutaric aciduria type I (GA1) patients carrying pathogenic biallelic variants in GCDH

GCDH encodes for the enzyme catalyzing the sixth step of the lysine degradation pathway. Autosomal recessive variants in GCDH are associated with glutaric aciduria type I (GA1), of which a wide genotypic spectrum of pathogenic variants have been described. In this study, hiPSC lines derived from four GA1 patients with different genotypes were generated and fully characterized. Two patients carry compound heterozygous variants in GCDH, while the other two patients carry a variant in homozygosis. These hiPSC lines can significantly contribute to better understand the molecular mechanism underlying GA1 and provide excellent models for the development of new therapeutic strategies.

Molecular genetic analysis of candidate genes for glutaric aciduria type II in a cohort of patients from Queensland, Australia

Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation. GAII has been considered an autosomal recessive condition caused by pathogenic variants in the gene encoding electron-transfer flavoprotein ubiquinone-oxidoreductase (ETFDH) or in the genes encoding electron-transfer flavoprotein subunits A and B (ETFA and ETFB respectively). Variants in genes involved in riboflavin metabolism have also been reported. However, in some patients, molecular analysis has failed to reveal diagnostic molecular results. In this study, we report the outcome of molecular analysis in 28 Australian patients across the lifespan, 10 paediatric and 18 adult, who had a diagnosis of glutaric aciduria type II based on both clinical and biochemical parameters. Whole genome sequencing was performed on 26 of the patients and two neonatal onset patients had targeted sequencing of candidate genes. The two patients who had targeted sequencing had biallelic pathogenic variants (in ETFA and ETFDH). None of the 26 patients whose whole genome was sequenced had biallelic variants in any of the primary candidate genes. Interestingly, nine of these patients (34.6%) had a monoallelic pathogenic or likely pathogenic variant in a single primary candidate gene and one patient (3.9%) had a monoallelic pathogenic or likely pathogenic variant in two separate genes within the same pathway. The frequencies of the damaging variants within ETFDH and FAD transporter gene SLC25A32 were significantly higher than expected when compared to the corresponding allele frequencies in the general population. The remaining 16 patients (61.5%) had no pathogenic or likely pathogenic variants in the candidate genes. Ten (56%) of the 18 adult patients were taking the selective serotonin reuptake inhibitor antidepressant sertraline, which has been shown to produce a GAII phenotype, and another two adults (11%) were taking a serotonin-norepinephrine reuptake inhibitor antidepressant, venlafaxine or duloxetine, which have a mechanism of action overlapping that of sertraline. Riboflavin deficiency can also mimic both the clinical and biochemical phenotype of GAII. Several patients on these antidepressants showed an initial response to riboflavin but then that response waned. These results suggest that the GAII phenotype can result from a complex interaction between monoallelic variants and the cellular environment. Whole genome or targeted gene panel analysis may not provide a clear molecular diagnosis.

Clinico-Biochemical Spectrum of Pakistani Patients with Glutaric Aciduria Type 1 (GA1): Experience from a Specialised Biochemical Genetics Laboratory in Pakistan.

To evaluate the clinical, radiological, and biochemical features of glutaric aciduria Type 1 (GA1) patients identified through urine organic acid testing at a biochemical genetics laboratory (BGL) in Pakistan. Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from January 2013 to December 2022. Medical charts and urine organic acid (UOA) chromatograms of the patients presenting at the BGL from January 2013 to December 2022 were reviewed. Brain imaging was obtained where available. Variables were noted as per the objective and descriptive statistics were obtained. GA1 was found in 64 (0.4%) patients out of a total of 16,094 UOA requests for high-risk screening cases. The age of diagnosis ranged between one month and three years. The brain MRI findings revealed characteristic abnormalities such as cerebral atrophy, expanded CSF spaces, white matter abnormalities, and a distinct bat wings appearance, in cohesion with the results of biochemical testing. Sixty-four cases of GA1 from a single centre indicate a high frequency of the disorder in Pakistan. Late diagnosis emphasises the need for increased clinical awareness and preferably newborn screening to ensure optimal outcomes. Glutaric aciduria Type 1 (GA1), Brain imaging, UOA analysis, Glutaryl-CoA dehydrogenase (GCDH), Pakistan.

Dried Blood Spot Postmortem Metabolic Autopsy With Genotype Validation for Sudden Unexpected Deaths in Infancy and Childhood in Hong Kong.

Background Inborn errors of metabolism (IEM) are collectively rare but potentially preventable causes of sudden unexpected death (SUD) in infancy or childhood, and metabolic autopsy serves as the final tool for establishing the diagnosis. We conducted a retrospective review of the metabolic and molecular autopsy on SUD and characterized the biochemical and genetic findings. Methodology A retrospective review of postmortem metabolic investigations (dried blood spot acylcarnitines and amino acid analysis, urine metabolic profiling where available, and next-generation sequencing on a panel of 75 IEM genes) performed for infants and children who presented with SUD between October 2016 and December 2021 with inconclusive autopsy findings or autopsy features suspicious of underlying IEM in our locality was conducted. Clinical and autopsy findings were reviewed for each case. Results A total of 43 infants and children aged between zero days to 10 years at the time of death were referred to the authors' laboratories throughout the study period. One positive case of multiple acyl-CoA dehydrogenase deficiency was diagnosed. Postmortem reference intervals for dried blood spot amino acids and acylcarnitines profile were established based on the results from the remaining patients. Conclusions Our study confirmed the importance of metabolic autopsy and the advantages of incorporating biochemical and genetic testing in this setting.

Evaluation of the first 5 years of a glutaric aciduria type I neonatal screening programme in Asturias

Introduction. Neonatal screening of glutaric aciduria type 1 (GA-1) has brought radical changes in the course and outcomes of this disease. This study analyses the outcomes of the first 5 years (2015–2019) of the AGA1 neonatal screening programme in our autonomous community. Material. We conducted an observational, descriptive and retrospective study. All neonates born between January 1, 2015 and December 31, 2019 that participated in the neonatal screening programme were included in the study. The glutarylcarnitine (C5DC) concentration in dry blood spot samples was measured by means of tandem mass spectrometry applying a cut-off point of 0.25 µmol/L. Results. A total of 30 120 newborns underwent screening. We found differences in the C5DC concentration based on gestational age, type of feeding and hours of life at sample collection. These differences were not relevant for screening purposes. There were no differences between neonates with weights smaller and greater than 1500 g. Screening identified 2 affected patients and there were 3 false positives. There were no false negatives. The diagnosis was confirmed by genetic testing. Patients have been in treatment since diagnosis and have not developed encephalopathic crises in the first 4 years of life. Conclusions. Screening allowed early diagnosis of two cases of GA-1 in the first 5 years since its introduction in our autonomous community. Although there were differences in C5DC levels based on gestational age, type of feeding and hours of life at blood extraction, they were not relevant for screening.

Inherited metabolic disorders in Cyprus

Selective screening for inherited metabolic disorders (IMD) began in Cyprus in 1990. Over the last thirty-three years 7388 patients were investigated for IMD and 200 diagnoses were made (diagnostic yield 2.7%). The existence of a single laboratory of Biochemical Genetics for the whole island facilitated the creation of a national registry for IMD. The minimal prevalence of IMD in Cyprus is 53.3 cases per 100,000 live births. The most common group are disorders of amino acid metabolism (41.0%), followed by disorders of carbohydrate metabolism (16.5%), disorders of complex molecule degradation (16.5%), mitochondrial disorders (10.5%) and disorders of vitamin and co-factor metabolism (5.5%). Hyperphenylalaninaemia is the most common IMD (14.0%) followed by galactosaemia (7.0%), glutaric aciduria type I (5.5%) and MSUD (4.0%). Some disorders were found to have a relatively high incidence in specific communities, for example Sandhoff disease among the Cypriot Maronites and GM1 gangliosidosis in one particular area of the island. Other disorders were found to have a relatively higher overall incidence, compared to other Caucasian populations, for example galactosaemia, glutaric aciduria type I and MSUD, while fatty acid oxidation defects, Gaucher disease and classic PKU were found to have a relatively lower incidence. Molecular characterization of selected disorders revealed many novel genetic variants, specific to the Cypriot population.

162 Patient with Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) and Glutaric Aciduria Type 1 (GA1) Successfully treated with delayed Hematopoietic Stem Cell Transplant (HSCT)

162 Patient with Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) and Glutaric Aciduria Type 1 (GA1) Successfully treated with delayed Hematopoietic Stem Cell Transplant (HSCT)