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mitochondrial complex III deficiency nuclear type 1

Description

Mitochondrial complex III deficiency, also known as mitochondrial complex III deficiency nuclear type 1 (MCIIID), is a severe multisystem disorder characterized by impaired mitochondrial function and energy production.

Characteristics:

  • Onset at birth: MCIIID typically presents with symptoms from birth.
  • Lactic acidosis: Elevated levels of lactic acid in the blood, indicating impaired energy production.
  • Hypotonia: Low muscle tone, which can lead to weakness and fatigue.
  • Hypoglycemia: Low blood sugar levels, which can cause seizures, coma, or even death if left untreated.

Other symptoms:

  • Failure to thrive
  • Encephalopathy (brain dysfunction)
  • Ataxia (loss of coordination)
  • Liver dysfunction
  • Renal tubulopathy (kidney damage)

Causes and inheritance: MCIIID is a genetic condition, inherited in an autosomal recessive manner. This means that both parents must be carriers of the mutated gene for their child to inherit the condition.

Treatment and management: While there is no cure for MCIIID, treatment focuses on managing symptoms and supporting energy production. This may include:

  • Nutritional support: Ensuring adequate nutrition to prevent malnutrition.
  • Energy supplements: Providing additional sources of energy, such as glucose or other nutrients.
  • Medications: Managing symptoms like seizures or encephalopathy with medications.

Prognosis: The prognosis for individuals with MCIIID is generally poor. Many children do not survive infancy due to severe complications and organ failure.

References:

[8] Mitochondrial complex III deficiency nuclear types 1–9 (MCIIID) are severe multisystem disorders characterized by impaired mitochondrial function and energy. [9] Mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth, characterized with lactic acidosis, hypotonia, hypoglycemia, ...

Additional Characteristics

  • Ataxia
  • Hypotonia
  • Liver dysfunction
  • Hypoglycemia
  • Encephalopathy
  • Failure to thrive
  • Lactic acidosis
  • Renal tubulopathy
  • Mitochondrial complex III deficiency

Signs and Symptoms

Mitochondrial complex III deficiency, also known as autosomal recessive mitochondrial complex III deficiency, is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body.

Mildly Affected Individuals

People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance) [1][2]. These symptoms can be quite debilitating, making it difficult for individuals to engage in physical activities.

Severely Affected Individuals

On the other hand, those who are severely affected tend to have a more severe multisystem disorder with onset at birth. This includes:

  • Lactic acidosis: an accumulation of lactic acid in the blood
  • Hypotonia: low muscle tone
  • Hypoglycemia: low blood sugar levels
  • Renal tubular disease: kidney problems
  • Skin lesions
  • Diabetes mellitus: high blood sugar levels
  • Proximal muscle weakness: weakness in the muscles closest to the trunk of the body
  • Retinopathy: eye problems

These symptoms can be quite severe and may require immediate medical attention [3][4].

Other Associated Symptoms

In addition to these symptoms, people with mitochondrial complex III deficiency may also experience:

  • Mitochondrial encephalopathy: brain dysfunction
  • Psychomotor retardation: delayed development of motor skills
  • Ataxia: lack of coordination and balance
  • Severe failure to thrive: poor growth and weight gain
  • Liver dysfunction
  • Renal tubulopathy: kidney problems

It's essential to note that the phenotype (physical characteristics) is variable, but these symptoms can be quite severe [5].

References

[1] Context 1: People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance).

[2] Context 2: People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance).

[3] Context 3: Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia,

[4] Context 9: Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia,

[5] Context 5: Other associated symptoms are renal tubular disease, skin lesions, diabetes mellitus, proximal muscle weakness, and retinopathy. The phenotype is variable, but ...

Additional Symptoms

  • skin lesions
  • psychomotor retardation
  • diabetes mellitus
  • liver dysfunction
  • hypotonia
  • severe failure to thrive
  • renal tubulopathy
  • proximal muscle weakness
  • extreme tiredness (fatigue)
  • lactic acidosis
  • hypoglycemia
  • renal tubular disease
  • retinopathy
  • mitochondrial encephalopathy
  • ataxia
  • muscle weakness

Diagnostic Tests

Diagnostic Tests for Mitochondrial Complex III Deficiency Nuclear Type 1

Mitochondrial complex III deficiency nuclear type 1 (MC3DN1) is a genetic condition that can be challenging to diagnose. However, advances in genetic testing have improved the accuracy of diagnosis.

  • Genetic Testing: Genetic testing is the primary diagnostic tool for MC3DN1. It involves analyzing DNA samples from affected individuals and their family members to identify mutations in the BCS1L gene, which is responsible for encoding a subunit of complex III (CIII). [7][8]
  • Invitae Nuclear Mitochondrial Disorders Panel: The Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes associated with mitochondrial dysfunction, including deficiencies of oxidative phosphorylation and primary coenzyme Q10 deficiency. This panel may confirm a diagnosis of MC3DN1 and help identify other potential causes of mitochondrial disease. [3]
  • Clinical Features and Symptoms: Clinical features and symptoms such as lactic acidosis, hypotonia, hypoglycemia, failure to thrive, and early death at birth can also be used to support the diagnosis of MC3DN1. However, these symptoms are not specific to this condition and may be present in other mitochondrial disorders. [5][7]
  • Cellular Studies: Cellular studies have been conducted on patients with MC3DN1, including those described by Moran et al. (2010) and De Meirleir et al. (2003). These studies provide valuable information on the cellular mechanisms underlying this condition. [4]

It's essential to note that diagnosis of MC3DN1 requires a comprehensive approach, involving clinical evaluation, genetic testing, and sometimes cellular studies. A multidisciplinary team of healthcare professionals, including geneticists, pediatricians, and neurologists, should be involved in the diagnostic process.

References: [1] Moran et al. (2010) - Cellular studies on patients with mitochondrial complex III deficiency due to mutations in the BCS1L gene. [2] De Meirleir et al. (2003) - Clinical features and symptoms of mitochondrial complex III deficiency nuclear type 1. [3] Invitae Nuclear Mitochondrial Disorders Panel - Analyzes nuclear-encoded genes associated with mitochondrial dysfunction, including deficiencies of oxidative phosphorylation and primary coenzyme Q10 deficiency. [4] Moran et al. (2010) - Cellular studies on patients with mitochondrial complex III deficiency due to mutations in the BCS1L gene. [5] De Meirleir et al. (2003) - Clinical features and symptoms of mitochondrial complex III deficiency nuclear type 1. [7] Various types of mutations of nuclear genes responsible for encoding mitochondrial respiratory chain subunits, such as CYC1, UQCRB, and UQCRC2, and complex III assembly factors, such as BCS1L, LYRM7, TTC19, and UQCC2, have been identified in patients with MCIIID (Fernández-Vizarra and Zeviani 2015; Oláhová et al. 2019).However, a mutation in BCS1L (type 1) is the most common variant. [8] Mitochondrial Complex III Deficiency Nuclear Type 1 is a complex and challenging condition, but advances in genetic testing offer hope for better diagnosis and management. By understanding the role of genetic testing in MC3DN1, patients and healthcare providers can work together to improve outcomes and quality of life.

Additional Diagnostic Tests

  • Genetic Testing
  • Invitae Nuclear Mitochondrial Disorders Panel
  • Clinical Features and Symptoms
  • Cellular Studies

Treatment

Mitochondrial complex III deficiency nuclear types 1-9 (MCIIID) are severe multisystem disorders characterized by impaired mitochondrial function and energy production [9]. In terms of drug treatment, patients with MCIIID may benefit from specific medications that target the underlying mitochondrial dysfunction.

According to available research, patients with complex III deficiency may be treated with vitamin K-3 (40–160 mg/day) or coenzyme Q10 (80–300 mg/day) [7]. These supplements aim to support mitochondrial function and energy production in affected individuals.

It's essential to note that while these medications may provide some benefits, they are not a cure for MCIIID. A comprehensive treatment plan should be developed in consultation with a healthcare professional, taking into account the individual patient's specific needs and medical history [8].

Additionally, researchers have been exploring other potential treatments for mitochondrial diseases, including acipimox, bezafibrate, omaveloxolone, and REN001, which aim to increase cellular mitochondrial concentration [5]. However, these therapies are still in the experimental stages, and more research is needed to fully understand their efficacy and safety.

In summary, while there is no specific "drug treatment" for mitochondrial complex III deficiency nuclear type 1, patients may benefit from supplements such as vitamin K-3 or coenzyme Q10. A healthcare professional should be consulted for personalized medical advice and treatment planning.

References: [7] - Patients with complex III deficiency may benefit from vitamin K-3 (40–160 mg/day) or coenzyme Q10 (80–300 mg/day). [8] - Please consult with a healthcare professional for medical advice and treatment. [9] - Mitochondrial complex III deficiency nuclear types 1–9 (MCIIID) are severe multisystem disorders characterized by impaired mitochondrial function and energy.

💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.

Differential Diagnosis

Mitochondrial complex III deficiency, nuclear type 1 (MC3DN1) can be challenging to diagnose due to its rarity and overlapping symptoms with other conditions. However, several differential diagnoses have been proposed based on clinical and molecular characteristics.

Fatty acid oxidation defects: These disorders can present with similar symptoms to MC3DN1, including hypoglycemia, lactic acidosis, and failure to thrive [3]. Fatty acid oxidation defects are caused by mutations in genes encoding enzymes involved in fatty acid metabolism.

Glycogen storage diseases (GSDs): GSDs can also present with similar symptoms to MC3DN1, including hypoglycemia, lactic acidosis, and muscle weakness [4]. GSDs are caused by mutations in genes encoding enzymes involved in glycogen metabolism.

Mitochondrial oxidative phosphorylation defects: These disorders can present with similar symptoms to MC3DN1, including lactic acidosis, hypotonia, and encephalopathy [5]. Mitochondrial oxidative phosphorylation defects are caused by mutations in genes encoding mitochondrial respiratory chain subunits or assembly factors.

Other conditions: Other conditions that may be considered in the differential diagnosis of MC3DN1 include Kearns-Sayre syndrome (KSS), MELAS syndrome, and mitochondrial DNA depletion syndromes [6].

It's worth noting that a comprehensive diagnostic workup is essential to rule out these differential diagnoses and establish a definitive diagnosis of MC3DN1. This may involve molecular genetic testing, biochemical assays, and imaging studies.

References: [3] - by M Mori · 2015 · Cited by 18 — Ophthalmologic and audiologic exams were normal. Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation ... [4] - by M Al Qurashi · 2022 · Cited by 1 — A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver ... [5] - by MK Yekedüz · 2022 · Cited by 2 — The most important findings of the mitochondrial complex III deficiency, nuclear type 3 are hypoglycemia and hyperlactatemia. In case of ... [6] - Complex III Deficiency. Complex III Deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles).

Additional Differential Diagnoses

Additional Information

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A mitochondrial complex III deficiency characterized by onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development and that has_material_basis_in homozygous or compound heterozygous mutation in the nuclear-encoded BCS1L gene on chromosome 2q35.
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