Complete deficiency of mitochondrial trifunctional protein due to a novel mutation within the β-subunit of the mitochondrial trifunctional protein gene leads to failure of long-chain fatty acid β-oxidation with fatal outcome

Schwab, Karl Otfried; Ensenauer, Regina; Matern, Dietrich; Uyanık, Gökhan; Schnieders, Birgit; Wanders, Ronald J. A.; Lehnert, W.

doi:10.1007/s00431-002-1035-4

Cited by 22 publications

(7 citation statements)

References 27 publications

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“…9 However, the prognosis of earlyonset MTP deficiency appears to be poor with most patients dying early in infancy. 8 Furthermore, once symptomatic cardiomyopathy has developed, it may be impossible to stabilize or improve the patient's condition with disorders like LCHAD and MTP deficiency. 10 Therefore, prospective diagnosis as early in life as possible is desirable.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 MTP deficiency is an autosomal recessive inborn error with a 25% recurrence risk for each pregnancy. 8 Prenatal diagnosis can be undertaken in prospectively identified high-risk pregnancies by immunoblot analysis of MTP in chorionic villi. 8 In the present case with a family history of unexplained sudden infant death, appropriate genetic counselling of the family is important.…”

Section: Discussionmentioning

confidence: 99%

“…8 Prenatal diagnosis can be undertaken in prospectively identified high-risk pregnancies by immunoblot analysis of MTP in chorionic villi. 8 In the present case with a family history of unexplained sudden infant death, appropriate genetic counselling of the family is important. Pediatricians, neonatologists and obstetricians need to be aware of the existence of disorders of mitochondrial fatty acid β -oxidation.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial trifunctional protein deficiency in a lethal neonate

Yamazaki

Torigoe

Numata

et al. 2004

Pediatrics International

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mitochondrial trifunctional protein deficiency in a lethal neonate

Yamazaki

Torigoe

Numata

et al. 2004

Pediatrics International

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“…Although some studies have examined tissues directly, most have targeted accessible biological fluids such as urine, cerebrospinal fluid, plasma, and AF. [94][95][96] By the use of MS, several inborn errors of metabolism received increased attention: phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia, galactosemia, methylmalonic acidemia, propionic academia, isovaleric acidemia, mitochondrial respiratory chain disorders, medium-chain acyl-coenzyme A dehydrogenase deficiency, iron chain fatty acid oxidation disorders, Wilson disease, Smith-Lemli-Opitz syndrome, and lysosomal storage disorders. 97 The first attempts to apply MS for prenatal diagnosis of inherited metabolic diseases originated in the early 1980s.…”

Section: The Emerging Role Of Proteomics-ms In Diagnosing Inherited Gmentioning

confidence: 99%

Proteomics: A Novel Methodology to Complement Prenatal Diagnosis of Chromosomal Abnormalities and Inherited Human Diseases

Bahtiyar¹,

Copel²,

Mahoney³

et al. 2007

Amer J Perinatol

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The current revolution in biomedical sciences has raised new hope for early diagnosis, prevention, and treatment of human diseases. Recent advancements in genomics, proteomics, and other basic sciences are currently transforming the medical science, and offer the promise of answering many of the questions related to human diseases, including their early and accurate diagnosis. Profiling of biological fluids (i.e., serum, urine, amniotic fluid, and cerebrospinal fluid) has successfully identified relevant protein biomarkers that potentially can change early diagnosis and treatment of several medical conditions related to human pregnancy. Similarly, proteomics holds the promise to complement genomics to revolutionize screening and prenatal diagnosis of genetic conditions during early pregnancy. This article summarizes current technology and reviews the application of proteomics in diagnosis of genetic disorders during human pregnancy.

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“…MTP consists of heterooctamer (α4β4) possessing three different enzyme activities: long-chain enoyl-CoA hydrolase (LCEH) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) activities harbored by the α-subunit (HADHA), while β-subunit (HADHB) encode long-chain 3-ketoacyl-CoA thiolase (LCKT) [10]. Deficiency of MTP is an autosomal recessive disorder that exhibits characteristic features of cardiomyopathy, hypoketotic hypoglycemia, metabolic acidosis, sudden infant death, metabolic encephalopathy, liver dysfunction, axonal sensory neuropathy and pigmentary retinopathy [11-13]. …”

Section: Introductionmentioning

confidence: 99%

A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

et al. 2013

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BackgroundCharcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria.MethodsTo identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed.ResultsWES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn’t exhibit any other symptoms of the previously reported HADHB patients.ConclusionsThese data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB.

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Complete deficiency of mitochondrial trifunctional protein due to a novel mutation within the β-subunit of the mitochondrial trifunctional protein gene leads to failure of long-chain fatty acid β-oxidation with fatal outcome

Cited by 22 publications

References 27 publications

Mitochondrial trifunctional protein deficiency in a lethal neonate

Mitochondrial trifunctional protein deficiency in a lethal neonate

Proteomics: A Novel Methodology to Complement Prenatal Diagnosis of Chromosomal Abnormalities and Inherited Human Diseases

A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

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