BackgroundPompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms.MethodsAn expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities.ResultsThese guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring.ConclusionsThese guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

ThedaytimefastingofRamadanisobservedannuallyby millions of adult Muslims all over the world. Some may have mild, moderate or severe medical conditions. They may seek advice on feasibility and safety of fasting and/ ortheirmanagement.Physiciansoughttohaveaworking knowledgeaboutthereligiousrulesofRamadanfastand theirmedicalimplications.Inthisarticlewepresentaconcise summaryoftheproceedingsofaseriesofsymposia.Their objectivesweretoreviewtheeffectsofRamadanfastingon thehealthofMuslimpatientswithvariouschronicmedical conditionsandtoproposepracticalmanagementstrategies. An initial introductory Islamic perspective on fasting to setthesceneforthefollowingpresentations.Thereligious rulingsexcludingpatientswithacuteandchronicmedical conditionsfromfastingwerehighlighted.Therolesofthe medicalprofessionalinguidingpatientsonbestwaystomake

Aim: Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts’ recommendations on how to optimally diagnose and treat patients suffering from this disease. Methods: A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD. Results & conclusion: Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.

AimThe aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I).MethodsAn international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real‐world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested.ResultsAn algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler–Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) – 16 Hurler, nine Hurler–Scheie and seven Scheie patients – would have been referred earlier if the algorithm had been used.ConclusionThe expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment.

AimMucopolysaccharidosis type I is a lysosomal storage disorder that can result in significant disease burden, disability and premature death, if left untreated. The aim of this review was to elaborate on the diagnosis of mucopolysaccharidosis type I and the pros and cons of newborn screening.MethodsAn international working group was established to discuss ways to improve the early diagnosis of mucopolysaccharidosis type I. It consisted of 13 experts in paediatrics, rare diseases and inherited metabolic diseases from Europe and the Middle East.ResultsIt is becoming increasingly clearer that the delay between symptom onset and clinical diagnosis is considerable for mucopolysaccharidosis type I and other rare lysosomal storage disorders, despite numerous awareness campaigns since therapies became available. Diagnosis currently depends on recognising the signs and symptoms of the disease. The practice of newborn screening, which is being explored by pilot programmes around the world, enables early diagnosis and consequently early treatment. However, these studies have highlighted numerous new problems and pitfalls that must be faced before newborn screening becomes generally available.ConclusionNewborn screening for mucopolysaccharidosis type I offers the potential for early diagnosis and early pre‐symptomatic treatment, but existing hurdles need to be overcome.

We report a case of genetically confirmed molybdenum cofactor deficiency in an infant presenting with difficult to control neonatal seizures, and a severe cystic leukoencephalopathy on brain magnetic resonance imaging (MRI). This is a rare disease entity that can be easily missed or confused with hypoxic ischemic encephalopathy. Raising awareness regarding this condition has significant implications regarding genetic counseling, prognostication, and possibly medicolegal liability. We report a case confirmed by genetic testing that revealed a mutation previously unreported to the best of our knowledge. We discuss the clinical presentation, imaging findings, and review the literature on this under-recognized disease.

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures and developmental delay. DEEs are primarily attributed to genetic causes and an increasing number of cases have been correlated with variants in ion channel genes. In this study, we report a child with an early severe DEE. Whole exome sequencing showed a de novo heterozygous variant (c.4873–4881 duplication) in the SCN8A gene and an inherited heterozygous variant (c.952G > A) in the CACNA1H gene encoding for Nav1.6 voltage-gated sodium and Cav3.2 voltage-gated calcium channels, respectively. In vitro functional analysis of human Nav1.6 and Cav3.2 channel variants revealed mild but significant alterations of their gating properties that were in general consistent with a gain- and loss-of-channel function, respectively. Although additional studies will be required to confirm the actual pathogenic involvement of SCN8A and CACNA1H, these findings add to the notion that rare ion channel variants may contribute to the etiology of DEEs.

Glutaric aciduria type II (GA-II) is a rare autosomal recessive disease caused by defects in electron transfer flavoprotein (ETF), ultimately causing insufficiencies in multiple acyl-CoA dehydrogenase (MAD). 3-phosphoglycerate dehydrogenase (3-PHGDH) deficiency, is another rare autosomal disorder that appears due to a defect in the synthesis of L-serine amino acid. Several mutations of ETFDH and PHGDH genes have been associated with different forms of GA-II and serine deficiency, respectively. In this study, we report a unique case of GA-II with serine deficiency using biochemical, genetic, and in silico approaches. The proband of Syrian descent had positive newborn screening (NBS) for GA-II. At two years of age, the patient presented with developmental regression, ataxia, and intractable seizures. Results of amino acid profiling demonstrated extremely low levels of serine. Confirmatory tests for GA-II and whole exome sequencing (WES) were performed to determine the etiology of intractable seizure. Sequencing results indicated a previously reported homozygous missense mutation, c.679 C>A (p.Pro227Thr) in the ETFDH gene and a novel missense homozygous mutation c.1219 T>C (p.Ser407Pro) in the PHGDH gene. In silico tools predicted these mutations as deleterious. Here, the clinical and biochemical investigations indicate that ETFDH:p.Pro227Thr and PHGDH:p.Ser407Pro variants likely underlie the pathogenesis of GA-II and serine deficiency, respectively. This study indicates that two rare autosomal recessive disorders should be considered in consanguineous families, more specifically in those with atypical presentation.