Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy,dysmorphic features,and hepatic dysfunction

AimMOGS mutations cause congenital disorders of glycosylation type IIb (CDG-IIb or GCS1-CDG). The specific manifestations caused by the mutations in this gene remain unknown. We aimed to describe the clinical features of CDG- IIb and the effectiveness of urinary oligosaccharide analysis in the diagnosis of CDG- IIb.MethodsPatient 1 was analyzed with whole-exome sequencing (WES) to identify the causative gene of intractable epilepsy and severe developmental delay. After detecting MOGS mutation in patient 1, we analyzed patients 2 and 3 who were siblings and had clinical features similar to those in patient 1. Urinary oligosaccharide analysis was performed to confirm CDG- IIb diagnosis in patient 1. The clinical features of these patients were analyzed and compared with those in eight published cases.ResultsOur three patients presented with early infantile epileptic encephalopathy, generalized hypotonia, hepatic dysfunction and dysmorphic features. In two cases, compound heterozygous mutations in MOGS were identified by WES. Isolation and characterization of the urinary oligosaccharide was performed in one of these cases to confirm the diagnosis of CDG-IIb. Although the isoelectric focusing of transferrin (IEF-T) of serum in this patient was normal, urinary excretion of Hex₄ corresponding to Glc₃Man was observed by mass spectrometry.ConclusionThis report provides clinical manifestations of CDG-IIb with MOGS mutation. CDG-IIb shows a normal IEF profile of serum transferrin and cannot be detected by structural analysis of the patient’s glycoproteins. Characterization of urinary oligosaccharides should be considered to detect this disorder.     

MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus

Deletion of the monoamine oxidase (MAO)-A and MAO-B was detected in two male siblings and in their mother. The approximately 800-kb deletion, extending from about 43.0 MB to 43.8 MB, was detected by array comparative genomic hybridization analysis. The MAOA and MAOB genes were included in the deletion, but the adjacent Norrie disease gene, NDP, was not deleted. The boys had short stature, hypotonia, severe developmental delays, episodes of sudden loss of muscle tone, exiting behavior, lip-smacking and autistic features. The serotonin levels in their cerebrospinal fluid were extremely elevated. Another set of siblings with this deletion was reported previously. We propose recognition of MAOA/B deletion syndrome as a distinct disorder.     

Cerebral palsy-definition, classification, etiology and early diagnosis

Cerebral palsy is a common neurodevelopmental condition encountered by pediatricians. The condition may present itself in many diferent clinical spectra. The etiological and risk factors are many and an awareness of the interplay of multiple factors in the causation of CP is crucial. In many cases, the cause of Cerebral palsy may not be apparent. Cerebral palsy is invariably associated with many deficits such as mental retardation, speech and language and oromotor problems. A thorough neurodevelopmental assessment of the child with Cerebral Palsy should include evaluation of associated deficits so that a comprehensive early intervention program an be planned and executed.     

Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a genetic disorder that occurs when there is a deletion in paternal chromosome 15. This rare disorder occurs in 1 in 15,000 births and affects all sex, races, or ethnicities. The clinical presentation includes hypotonia in infant with poor suck which can lead to failure to thrive, feeding difficulties, weak cry, hypogonadism with resulting hormonal imbalance, short stature, childhood obesity, hyperphagia, behavioral problems, and skin picking. Research shows that the chromosomal abnormality in PWS leads to dysfunction of the hypothalamic system. The hypothalamus modulates our endocrine and hormonal system via its connection with the pituitary gland. This dysfunction leads to inability to modulate one's hormones, appetite, weight, and emotions. The team responsible for the care of infants with PWS help guide families from the very beginning of establishing a diagnosis and the implications of the long-term complications from PWS.     

Neurological examination of the newborn

Sophisticated technology for neurodiagnosis supplements, but does not replace, the neurological examination. Physical examination remains the standard for assessing the normal or abnormal function of the nervous system, the localization of neurological injury, and the severity of impairment. An experienced examiner can rapidly perform this assessment and then exercise the best judgement in selecting laboratory investigations.     

Myopathology in patients with a Noonan phenotype

Two patients with a Noonan phenotype and progressive hypertrophic obstructive cardiomyopathy are described, in whom abnormal histopathological changes in striated musculature were detected. In both patients an increased density of muscle spindles was found at biopsy. The significance of an increased density of muscle spindles in patients with Noonan phenotype can only be speculated. The question is raised of whether these changes are a distinct feature within the spectrum of patients with Noonan phenotype. Received: 10 July 1995 / Revised, accepted: 3 June 1996     

Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype

BackgroundAromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case reportWe report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.InterpretationOur cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment.