Variant maple syrup urine disease (MSUD)—The entire spectrum

Simon, Éva; Flaschker, N.; Schadewaldt, Peter; Langenbeck, U.; Wendel, U.

doi:10.1007/s10545-006-0276-1

Cited by 53 publications

(39 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As discussed earlier, inherited mutations of BCKD subunits cause MSUD in humans with a spectrum of severity. According to the variation in clinical consequences and genetic testing, human MSUD is categorized into 5 types: classic, intermediate, intermittent, thiamine responsive, and E3 deficient (8,34). Our data clearly demonstrate that loss of PP2Cm leads to a metabolic and phenotypic abnormality characteristic of intermittent or intermediate types of human MSUD.…”

Section: Figurementioning

confidence: 67%

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells

Lü

Sun²,

She³

et al. 2009

J. Clin. Invest.

196

192

View full text Add to dashboard Cite

The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain-α-ketoacid dehydrogenase (BCKD) complex, the rate-limiting step in their metabolism. BCKD is inhibited by phosphorylation of its E1α subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates. Loss of PP2Cm completely abolished substrate-induced E1α dephosphorylation both in vitro and in vivo. PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar to the intermittent or intermediate types of human maple syrup urine disease (MSUD), a hereditary disorder caused by defects in BCKD activity. These results indicate that PP2Cm is the endogenous BCKD phosphatase required for nutrient-mediated regulation of BCKD activity and suggest that defects in PP2Cm may be responsible for a subset of human MSUD.

show abstract

Section: Figurementioning

confidence: 67%

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells

Lü

Sun²,

She³

et al. 2009

J. Clin. Invest.

196

192

View full text Add to dashboard Cite

show abstract

“…In patients with variant MSUD, a continuum of clinical severity exists [14]. Subjects with a more severe, so-called intermediate, variant have markedly increased BCAA levels and neurological impairment, but do not have catastrophic illness with coma in the neonatal period.…”

Section: Introductionmentioning

confidence: 99%

Recall rate and positive predictive value of MSUD screening is not influenced by hydroxyproline

Fingerhut

2008

Eur J Pediatr

View full text Add to dashboard Cite

Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder caused by the deficiency of the branched-chain 2-oxo acid dehydrogenase (BCOA-DH) complex. The worldwide incidence is approximately 1 in 185,000. MSUD is integrated in many "expanded" newborn screening (NBS) programs that use electrospray ionization tandem mass spectrometry (ESI-MS/MS). Elevated leucine, isoleucine, and alloisoleucine in the dried blood samples (DBS) of newborns are diagnostic parameters. However, with the applied method, it is not possible to distinguish the amino acids from each other, and also not from the other isobaric amino acid, hydroxyproline. While the branched chain amino acids (BCAA) leucine, isoleucine, and alloisoleucine are no diagnostic problem, because they are all elevated in MSUD patients, and, rather, increase the diagnostic sensitivity and specificity, hydroxyproline may cause false-positive screening results. Hydroxyproline is elevated in the benign familial condition hyperhydroxyprolinemia, which needs no medical intervention. The detection of cases with hyperhydroxyprolinemia have formerly been reported from screening programs that used thin-layer chromatography for phenylketonuria (PKU) screening, and, recently, two more cases have been reported, detected by ESI-MS/MS-based NBS. However, the detection of non-diseases is a heavy burden for screening programs and should be avoided if possible. With optimal settings for the quantitation of BCAAs and interpretation rules, elevated hydroxyproline should not cause false-positive screening results.

show abstract

“…Clinically, there is hypertonicity and muscular rigidity with opisthotonus posture. Neurological fi ndings are often mistaken for sepsis or meningitis, and death occurs if untreated 4 . In our case of also we thought of clinically sepsis only.…”

Section: Discussionmentioning

confidence: 99%

Role of Diffusion Weighted MRI in Maple Syrup Urine Disease: Rare Cause of Neonatal Metabolic Encephalopathy

Shah

Nirula

Shah

2013

J. Nepal Paedtr. Soc.

View full text Add to dashboard Cite

The newborn presenting with neurological symptoms such as seizures or lethargy due to inborn error of metabolism is an important problem. Maple syrup urine disease (MSUD) is an inherited genetic disease, caused by a deficiency of the catalytic components of α-ketoaciddehydrogenase complex, which is responsible for the catabolism of branched-chain amino acids. The purpose of this case report is to show diffusion-weighted imaging (DWI) MRI findings of acute phase of classic form of MSUD in a newborn although this imaging findings are rare but very typical, known as "MSUD oedema".

show abstract

Variant maple syrup urine disease (MSUD)—The entire spectrum

Abstract: A continuum of clinical severity from asymptomatic to very severe (border to classic) exists in variant MSUD. Apart from newborns with classic MSUD, also those with variant forms benefit from early diagnosis and start of adequate treatment.

Cited by 53 publications

References 11 publications

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells

Recall rate and positive predictive value of MSUD screening is not influenced by hydroxyproline

Role of Diffusion Weighted MRI in Maple Syrup Urine Disease: Rare Cause of Neonatal Metabolic Encephalopathy

Contact Info

Product

Resources

About