Holocarboxylase synthetase deficiency pre and post newborn screening

Donti, Taraka; Blackburn, Patrick R.; Atwal, Paldeep S.

doi:10.1016/j.ymgmr.2016.03.007

Cited by 41 publications

(19 citation statements)

References 5 publications

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“…To the less astute clinician, the reassuring ‘comprehensive evaluation’ can be misleading as it suggests this is the only test that is needed. This point highlights the need for medical genetics input in these complex cases and reminds us genetic testing can be complex and confusing [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] .…”

Section: Discussionmentioning

confidence: 96%

Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement

Mohammad¹,

Bruno²,

Hines³

et al. 2018

Molecular Genetics and Metabolism Reports

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Sialidosis is an autosomal recessive lysosomal storage disease caused by pathogenic variants in NEU1 which encodes lysosomal sialidase (neuraminidase 1). Lysosomal neuraminidase catalyzes the removal of terminal sialic acid molecules from glycolipids, glycoproteins and oligosaccharides. Sialidosis is classified into two types, based on phenotype and age of onset. Patients with the milder type 1 typically present late, usually in the second or third decade, with myoclonus, ataxia and visual defects. Type 2 is more severe and presents earlier with coarse facial features, developmental delay, hepatosplenomegaly and dysostosis multiplex. Presentation and severity of the disease are related to whether lysosomal sialidase is inactive or there is some residual activity. Diagnosis is suspected based on clinical features and increased urinary bound sialic acid excretion and confirmed by genetic testing showing pathogenic variants in NEU1. We report a patient with type 1 sialidosis who presented mainly with ataxia and both generalized and myoclonic seizures but no visual involvement. Whole exome sequencing of the proband detected compound heterozygous likely pathogenic variants (S182G and G227R) in NEU1.

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Section: Discussionmentioning

confidence: 96%

Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement

Mohammad¹,

Bruno²,

Hines³

et al. 2018

Molecular Genetics and Metabolism Reports

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“…however longitudinal monitoring which includes rate of progression to assess whether underlying genotype is affecting the phenotype should be performed at a future date to con rm this prior observation. Mechanistically regarding genotype-phenotype correlations in biochemical genetics, more severe mutations tend to result in less functional enzyme and thus infer a more severe phenotype; this is observed in other genetic disorders of enzymatic function and metabolism (2,(20)(21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

The Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS)

Atwal

Midei

Adams

et al. 2020

Preprint

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Background: INAD is an autosomal recessive neurogenetic disorder caused by biallelic pathogenic variants in PLA2G6. The downstream enzyme, iPLA2, plays a critical role in cell membrane homeostasis by helping to regulate levels of phospholipids. The clinical presentation occurs between 6 months and 3 years with global developmental regression, hypotonia, and progressive spastic tetraparesis. Progression is often rapid, resulting in severe spasticity, visual impairment, and cognitive decline, with many children not surviving past the first decade of life. To date, no accepted tool for assessing the severity of INAD exists; other commonly used scales (e.g. CHOP-INTEND, Modified Ashworth, Hammersmith Functional Motor Scale) do not accurately gauge the current severity of INAD, nor are they sensitive/specific enough to monitor disease progression. Finally, these other scales are not appropriate, because they do not address the combination of CNS, peripheral nerve, and visual pathology that occurs in children with INADMethods: We have developed and validated a structured neurological examination for INAD (scored out of 80). The examination includes six main categories of pediatric developmental evaluation: 1) gross motor-and-truncal-stability skills, 2) fine motor skills, 3) bulbar function, 4) ocular function, 5) temporo-frontal function, and, 6) Functional evaluation of the autonomic nervous system. A cohort of patients diagnosed with INAD were followed prospectively to validate the score against disease severity and disease progression. Results: We show significant correlation between the total neurological assessment score and months since symptom onset with a statistically significant (p = 6.7 x 10-07) correlation between assessment score and disease onset. As hypothesized, the coefficient of months-since-symptom-onset is strongly negative, indicating a negative correlation between total score and months since symptom onset.Conclusion: We have developed and validated a novel neurological assessment score in INAD that demonstrates strong correlation with disease severity and disease progression.

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“…253270.-Holocarboxylase synthetase deficiency is a life-threatening early-onset form of multiple carboxylase deficiency that is caused by a defect in holocarboxylase synthase activity (32). The estimated incidence is one in 200 000 individuals.…”

Section: Holocarboxylase Synthetase Deficiency: Omimmentioning

confidence: 99%

Neuroimaging Findings of Organic Acidemias and Aminoacidopathies

Reddy¹,

Calloni²,

Vernon³

et al. 2018

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Although individual cases of inherited metabolic disorders are rare, overall they account for a substantial number of disorders affecting the central nervous system. Organic acidemias and aminoacidopathies include a variety of inborn errors of metabolism that are caused by defects in the intermediary metabolic pathways of carbohydrates, amino acids, and fatty acid oxidation. These defects can lead to the abnormal accumulation of organic acids and amino acids in multiple organs, including the brain. Early diagnosis is mandatory to initiate therapy and prevent permanent long-term neurologic impairments or death. Neuroimaging findings can be nonspecific, and metabolism- and genetics-based laboratory investigations are needed to confirm the diagnosis. However, neuroimaging has a key role in guiding the diagnostic workup. The findings at conventional and advanced magnetic resonance imaging may suggest the correct diagnosis, help narrow the differential diagnosis, and consequently facilitate early initiation of targeted metabolism- and genetics-based laboratory investigations and treatment. Neuroimaging may be especially helpful for distinguishing organic acidemias and aminoacidopathies from other more common diseases with similar manifestations, such as hypoxic-ischemic injury and neonatal sepsis. Therefore, it is important that radiologists, neuroradiologists, pediatric neuroradiologists, and clinicians are familiar with the neuroimaging findings of organic acidemias and aminoacidopathies. RSNA, 2018.

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Holocarboxylase synthetase deficiency pre and post newborn screening

Cited by 41 publications

References 5 publications

Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement

Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement

The Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS)

Neuroimaging Findings of Organic Acidemias and Aminoacidopathies

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