Further Studies of Hyperlysinemia

Woody, Norman C.

doi:10.1001/archpedi.1966.02090150121014

Cited by 13 publications

(14 citation statements)

References 3 publications

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“…Four children with hyperlysinemia excreted amounts of pipecolic acid that demonstrated that a pathway for lysine degradation, via pipecolic acid to a-aminoadipic acid, was functioning in these patients, that this pathway had been pressed into maximal utilization by the high tissue lysine levels of these patients, and that in hyperlysinemic patients this pathway was a secondary one for lysine degradation. These findings support the thesis [12,17,50,51] that the major path of lysine degradation in man is through conversion (by lysine-ketoglutarate reductase) of lysine to saccharopine en route to a-aminoadipic acid.…”

Section: Discussionsupporting

confidence: 89%

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Excretion of Pipecolic Acid by Infants and by Patients with Hyperlysinemia

Woody

Pupene

1970

Pediatr Res

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Pediat. Res. 4: 89-95 (1970) ExtractPipecolic acid has been found in urine from normal infants and from children with hyperlysinemia. The reaction of pipecolic acid with ninhydrin reagent, using separation procedures in automated ion-exchange systems for amino acid analysis, produced a color constant of low value (1.21 compared with 27.6 for leucine) that could be overlooked in routine analyses of physiological fluids. Pipecolic acid was present in the urine from: four premature infants (6-23 days old) 1.2-8.1 ,«g/ m g creatinine; two of four term infants (3-5 days old) 1.3 and 2.1 ,«g/mg creatinine; and one of four infants (4-11 months old) 2.1 /jg/mg. No pipecolic acid was found in the urines of four infants 14-30 months old. In patients with hyperlysinemia, the amounts of pipecolic acid excreted in the urine were: 3.1 ^g/mg creatinine (4-year-old girl); 5.2 //g/rng creatinine (6-year-old boy); 6.2 /"g/mg creatinine (9-year-old girl); and 4.8 ,ug/mg creatinine (12-year-old girl). SpeculationThe low color yield of pipecolic acid, when separated by standard automated ion-exchange analysis methods, may account for past failures to detect small amounts of this substance in physiological fluids. Amounts of pipecolic acid excreted by young infants and by children with hyperlysinemia indicate that a degradation pathway for lysine, via pipecolic acid to a-aminoadipic acid, is operative in man. Introductionamino acids by infants, children, and adults [2,4,8-10, 14, 16, 19, 21-23, 25, 26, 28, 30, 36, 39, 41-45, 47, 48] Pipecolic acid has been shown to be a product of lysine make no mention of pipecolic acid as a normal urinary metabolism in rats [31][32][33], guinea pigs [5,20,34], constituent, but JAGENBURG [18] detected pipecolic and turkeys [6,7]. It has been detected in plants [53] acid in urine from infants less than 1 year old; however, and is derived from lysine in some of them [15,24]. he was unable to find it in urine of adults. Pipecolic Certain microorganisms form pipecolic acid from a-acid also has been found in the urine of a child with aminoadipic acid [3]; others derive it from lysine by hyperlysinemia [49] and in urine of patients with pathways similar to those described for mammals [20, hyperthyroidism [38]. GHADIMI et al. [13], however,35].attempting to detect pipecolic acid in urine from norReports of the presence of pipecolic acid in human mal premature infants, infants, and adults, and from urine are conflicting. Numerous studies of excretion of patients with hyperlysinemia were unsuccessful, and

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Section: Discussionsupporting

confidence: 89%

“…Studies bearing on lysine metabolism by the human [1,12,17,50,51] indicate that alternate pathways for lysine degradation exist ( fig. 3), and that the pathway (II) via conversion of lysine to saccharopine by lysineketoglutarate reductase is probably the major one.…”

Section: Discussionmentioning

confidence: 99%

Excretion of Pipecolic Acid by Infants and by Patients with Hyperlysinemia

Woody

Pupene

1970

Pediatr Res

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“…This table restates, in somewhat more de- Table II. Lysine and lysine metabolites in urine 1 tail, data previously gathered in collaboration with others [7]. Of interest here is the fact that the percentage excreted in the urine as lysine metabolites is about the same for all the subjects although excretion of 14 CO 2 and urinary lysine varied markedly between the controls and patients with hyperlysinemia.…”

Section: Resultsmentioning

confidence: 73%

“…This was prepared, sterilized, and tested for purity as previously described [7]. Urines were collected every 1.5 hr for 12 hr; 10% thymol in isopropanol was added, and specimens were stored at -50° until ana-WOODY AND PUPENE lyzed.…”

Section: Materials and Alctliodsmentioning

confidence: 99%

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Derivation of Pipecolic Acid from L-Lysine by Familial Hyperlysinemics

Woody

Pupene

1971

Pediatr Res

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Normal children and children with familial hyperlysinemia were given L-(U-14 C)-lysine by intramuscular injection. Labeled pipecolic acid and A'-a-acetyllysine were found in the urines, indicating derivation of these substances from lysine. The percentage of administered radioactivity excreted as 14 CO 2 and as urinary lysine varied markedly between controls and those with hyperlysinemia, but the percentage excreted in the urine in the form of various metabolites of lysine was about the same for controls (1.7-2.4) and those with hyperlysinemia (1.9-2.2). The proportion of these urinary lysine metabolites comprising pipecolic acid, homocitrulline, homoarginine, iV-e-acetyllysine and jV-a-acetyllysine was two to seven times greater for children with hyperlysinemia than for controls. These findings suggest that these pathways for lysine degradation are being maximally utilized by patients with familial hyperlysinemia who cannot degrade lysine by way of the saccharopine pathway. Speculation

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A case of hyperlysinemia identified by urine newborn screening

Yeganeh,

Auray‐Blais,

Maranda

et al. 2023

JIMD Reports

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Hyperlysinemia is a rare autosomal recessive deficiency of 2‐aminoadipic semialdehyde synthase (AASS) affecting the initial step in lysine degradation. It is thought to be a benign biochemical abnormality, but reports on cases remain scarce. The description of additional cases, in particular, those identified without ascertainment bias, may help counseling of new cases in the future. It may also help to establish the risks associated with pharmacological inhibition of AASS, a potential therapeutic strategy that is under investigation for other inborn errors of lysine degradation. We describe the identification of a hyperlysinemia case identified in the Provincial Neonatal Urine Screening Program in Sherbrooke, Quebec. This case presented with a profile of cystinuria but with a very high increase in urinary lysine. A diagnosis of hyperlysinemia was confirmed through biochemical testing and the identification of biallelic variants in AASS. The p.R146W and p.T371I variants are novel and affect the folding of the lysine‐2‐oxoglutarate domain of AASS. The 11‐month‐old boy is currently doing well without any therapeutic interventions. The identification of this case through newborn urine screening further establishes that hyperlysinemia is a biochemical abnormality with limited clinical consequences and may not require any intervention.

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Further Studies of Hyperlysinemia

Cited by 13 publications

References 3 publications

Excretion of Pipecolic Acid by Infants and by Patients with Hyperlysinemia

Excretion of Pipecolic Acid by Infants and by Patients with Hyperlysinemia

Derivation of Pipecolic Acid from L-Lysine by Familial Hyperlysinemics

A case of hyperlysinemia identified by urine newborn screening

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