Quick Mitochondrial Disorder Cards

Mitochondrial Disease (General)

• Most Identifiable Symptom: Multisystem disease – especially neurological symptoms, musculoskeletal disease, hearing loss, vision loss. Progressive.

• Key Biochemical Finding: Lactic acidosis. Plasma amino acids may show elevated alanine and proline.

• Treatment: Primarily supportive. "Mito cocktail" (Carnitine, CoQ10, Thiamine, Riboflavin, etc.). Ketogenic diet may alleviate severe seizures.

Pyruvate Dehydrogenase (PDH) Deficiency

• Most Identifiable Symptom: Leigh syndrome: progressive neurological disorder within first year of life (psychomotor regression, hypotonia, seizures).

• PDHA1, PDK3 (X-linked); PDHB, PDHX, PDP1, DLAT, DLD (autosomal recessive).

• Key Biochemical Finding: Elevated lactate, elevated lactate to pyruvate ratio.

• Treatment: (Not specified; falls under general mitochondrial supportive care).

Pyruvate Carboxylase (PC) Deficiency

• Most Identifiable Symptom: Variable phenotype - most common is severe infantile onset encephalopathy.

• Genetics : AR-inherited

• Key Biochemical Finding: Can present with mild-to-moderate hyperammonemia, elevated lysine, proline, and alanine with decreased glutamine.

• Treatment: (Not specified; falls under general supportive care).

Fumarase Deficiency

• Most Identifiable Symptom: Severe infantile encephalopathy.

• Gene: FH (Autosomal Recessive). Heterozygous variants cause HLRCC.

• Key Biochemical Finding: (Not specified beyond general TCA dysfunction).

• Treatment: (Not specified; falls under general supportive care).

mtDNA Depletion Disorders

• Most Identifiable Symptom: Infantile lactic acidosis and encephalopathy; prolonged acidosis is fatal. Can include Leigh syndrome, myopathy, organ failure.

• Key Biochemical Finding: (Implied severe lactic acidosis).

• Treatment: (Not specified; falls under general supportive care).

• Cause: Variants in nuclear genes important for mitochondrial synthesis or mtDNA replication (Autosomal Recessive).
  

Kearns-Sayre Syndrome (KSS)

• Most Identifiable Symptom: Clinical triad <20yrs: Progressive ophthalmoplegia, Pigmentary retinopathy, Heart block.

• Mutation Type: Large-scale deletions in mitochondrial DNA (mtDNA).

• Key Biochemical Finding: (Caused by large mtDNA deletion; lactic acidosis common).

• Treatment: (Not specified; falls under general supportive care).

Pearson Syndrome

• Most Identifiable Symptom: Before 1yr: Pancytopenia and sideroblastic anemia that spontaneously resolve. Pancreatic dysfunction, lactic acidosis.

• Mutation Type: Large-scale deletions in mitochondrial DNA (mtDNA).

• Key Biochemical Finding: (Caused by large mtDNA deletion).

• Treatment: (Not specified; falls under general supportive care).

Chronic Progressive External Ophthalmoplegia (CPEO)

• Most Identifiable Symptom: Adolescence to adult onset: Ptosis, Ophthalmoplegia (extraocular muscle paralysis).

• Mutation Type: Large-scale deletions in mitochondrial DNA (mtDNA).

• Key Biochemical Finding: (Caused by large mtDNA deletion).

• Treatment: Life expectancy is typically normal. (Implied supportive care).

MERRF (Myoclonic Epilepsy with Ragged Red Fibers)

• Most Identifiable Symptom: Childhood to adolescence onset myoclonus and generalized seizures. Abnormal muscle cells that appear frayed and stained red due to abnormalities in mitochondrial accumulation.

• Mutation: m.8344A>G in MT-TK

• Key Biochemical Finding: (Caused by mtDNA point mutation, commonly m.8344A>G in MT-TK).

• Treatment: (Not specified; falls under general supportive care).

MELAS

• Most Identifiable Symptom: Stroke-like episodes (migraine-like episodes with imaging consistent with infarct). Can present with myopathy, cognitive decline, seizures.

• Mutation: m.3243A>G in MT-TL1

• Key Biochemical Finding: Lactic acidosis (elevated with episodes or chronically). Commonly caused by m.3243A>G in MT-TL1.

• Treatment: (Not specified; falls under general supportive care).

MIDD

• Most Identifiable Symptom: Diabetes and deafness.

• Mutation: m.3243A>G in MT-TL1 (same mutation as MELAS).

• Key Biochemical Finding: Commonly associated with the m.3243A>G mutation.

• Treatment: (Not specified; falls under general supportive care).

MNGIE

• Most Identifiable Symptom: Neuro-gastrointestinal encephalomyopathy (symptoms not detailed further in PPT).

• Key Biochemical Finding: (Caused by mtDNA mutation).

• Treatment: (Not specified; falls under general supportive care).

NARP + Leigh Syndrome

• Most Identifiable Symptom: Neuropathy, Ataxia, Retinitis Pigmentosa.

• Mutation: m.8993T>G/C in MT-ATP6

• Key Biochemical Finding: Commonly caused by m.8993T>G/C in MT-ATP6.

• Treatment: (Not specified; falls under general supportive care).

LHON (Leber’s)

• Most Identifiable Symptom: Adolescence to adult onset bilateral painless central vision loss.

• Mutations: m.11778G>A, m.3460G>A, m.14484T>C

• Key Biochemical Finding: ONLY mitochondrial disorder caused by a homoplasmic variant (common mutations: m.11778G>A, m.3460G>A, m.14484T>C).

• Treatment: (Not specified; falls under general supportive care).