Hyperlysinemias

Last update 23 Jan 2025

Basic Info

Synonyms

ALPHA-AMINOADIPIC SEMIALDEHYDE SYNTHASE DEFICIENCY, Alpha Aminoadipic Semialdehyde Deficiency Disease, Alpha-Aminoadipic Semialdehyde Deficiency Disease

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Introduction

A group of inherited metabolic disorders which have in common elevations of serum LYSINE levels. Enzyme deficiencies of alpha-aminoadipic semialdehyde dehydrogenase and the SACCHAROPINE DEHYDROGENASES have been associated with hyperlysinemia. Clinical manifestations include mental retardation, recurrent emesis, hypotonia, lethargy, diarrhea, and developmental delay. (From Menkes, Textbook of Child Neurology, 5th ed, p56)

Clinical Trials associated with Hyperlysinemias

NCT00779753

/ CompletedNot ApplicableIIT

Determination of Lysine Requirement in the Parenterally Fed Neonate

The purpose of this study is to establish the parenteral lysine requirements for neonates.

Start Date01 Jul 2008

Sponsor / Collaborator

The Hospital for Sick Children

100 Clinical Results associated with Hyperlysinemias

100 Translational Medicine associated with Hyperlysinemias

0 Patents (Medical) associated with Hyperlysinemias

224

Literatures (Medical) associated with Hyperlysinemias

01 Dec 2024·Cell Reports

Restricting lysine normalizes toxic catabolites associated with ALDH7A1 deficiency in cells and mice

Article

Author: Kehinde, Abisola Z ; Towriss, Morgan ; Koe, Jessica C ; Ciernia, Annie V ; Johal, Amritpal S ; Hewton, Keeley G ; Parker, Seth J ; Al-Shekaili, Hilal H ; Thomson, Sarah B ; Leavitt, Blair ; Abedrabbo, Muna

Lysine metabolism converges at α-aminoadipic semialdehyde dehydrogenase (ALDH7A1). Rare loss-of-function mutations in ALDH7A1 cause a toxic accumulation of lysine catabolites, including piperideine-6-carboxylate (P6C), that are thought to cause fatal seizures in children unless strictly managed with dietary lysine reduction. In this study, we perform metabolomics and expression analysis of tissues from Aldh7a1-deficient mice, which reveal tissue-specific differences in lysine metabolism and other metabolic pathways. We also develop a fluorescent biosensor to characterize lysine transporter activity and identify competitive substrates that reduce the accumulation of lysine catabolites in ALDH7A1-deficient HEK293 cells. Lastly, we show that intravenous administration of lysine α-oxidase from Trichoderma viride reduces lysine and P6C levels by >80% in mice. Our results improve our understanding of lysine metabolism and make inroads toward improving therapeutic strategies for lysine catabolic disorders.

01 Aug 2024·Seizure: European Journal of Epilepsy

Hyperlysinemia, an ultrarare inborn error of metabolism: Review and update

Review

Author: Pascarella, F ; Battini, R ; Alessandrì, M G ; Santangelo, A ; Vetro, A ; Pochiero, F ; Pasquariello, R ; Bonuccelli, A ; Marinella, G ; Orsini, A

Familial hyperlysinemia is a rare autosomal recessive disorder due to defects of the AASS (α-aminoadipate δ-semialdehyde synthase) gene, which encodes for a bifunctional enzyme. Two types of hyperlysinemia have been identified namely type 1, due to the deficit of the alfa-ketoglutarate activity, and type 2, due to the deficit of the saccharopine dehydrogenase activity.METHODSTo better characterize the phenotypic spectrum of familial hyperlysinemia type 1, we conducted a systematic review of cases in the literature following PRISMA guidelines. We selected 16 articles describing 23 patients with hyperlysinemia type 1, twelve of whom with homozygous or compound heterozygous mutations in AASS gene. We also included a novel patient with a homozygous c.799C>T; p.(Arg267Cys) mutation in AASS gene. We collected genetic, clinical, brain imaging and electroencephalogram (EEG) features when available.RESULTSThe phenotype of this disease is heterogeneous, ranging from more severe forms with spastic tetraparesis, intellectual disability and epilepsy and mild-moderate forms with only intellectual disability or behavioural problem and/or epilepsy to normal clinical conditions. Only our patient has neuropathy unrelated to infectious event.CONCLUSIONSWe described the heterogeneous phenotypic spectrum of familial hyperlysinemia type 1 and we identified a new symptom, axonal neuropathy, never before described in this condition.

01 May 2024·JIMD Reports

Dietary management for pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency, a follow‐on from the international consortium guidelines

Article

Author: Drumm, Morgan ; van Wegberg, Annemiek M. J. ; Dixon, Marjorie ; Bernstein, Laurie ; Gaughan, Sommer ; Coughlin, Curtis R. ; van Karnebeek, Clara D. M. ; Millington, Chloe

AbstractPyridoxine‐dependent epilepsy (PDE‐ALDH7A1) is a neurometabolic disorder in the lysine metabolism pathway. In 2014 and 2021, the International PDE consortium published consensus guidelines about diagnosis and management. In this follow‐on, a literature review was performed and nutrition management was evaluated through an international dietary questionnaire with 40 respondents. This manuscript discusses consensus dietary statements and the practical provision of lysine reduction therapies. Results from the questionnaire, statements from the PDE consensus guidelines, new data from the literature, as well as clinical practice experience of the metabolic dietitian group form the basis of these updated practical diet recommendations. These dietary management recommendations can support dietitians, nutritionists, and physicians in initiation and monitoring of lysine reduction therapies for PDE‐ALDH7A1 patients and families.

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