Mitochondrial Disorder Flashcards

Primary Mitochondrial Disorder Flags

• Lactic acidosis

• Multisystemic disease

  • Neurological, musculoskeletal, hearing loss, vision loss, vision loss

• Progressive

General Mito Treatment

• Primarily supportive

• Lifestyle changes to prevent oxidative stress

• Keto diet to alleviate seizures and neuro disease

  • Mito cocktail

    • Carnitine

    • Coq10

    • B1 and B2

    • Arg, citrulline

    • Other vitamins

Diagnostic Challenges

• Nonspecific/sensitive testing, wide phenotypic specturm

• Medical management is very difficult (progressive symptoms, multisystem)

• Uncertain prognosis

TCA Disorders - PDH Deficiency

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

• Biochem findings : high lactate to pyruvate ratio

Symptoms, Leigh Syndrome

• Progressive neurological disease

• Poor feeding FTT

• Psychomotor regression

• Hypotonia, dystonia, ataxia

• Seizure

Brain MRI

• Cerebral atrophy and ventriculomegaly

• Dysgenesis/agenesis of corpus callosum (connective tissue for halves of the brain)

• T2 hyperintensities w/ basal ganglia involvement

Other

• Ptosis, cortical vision impairment

• High mortality and morbidity

PC Deficiency

• 1/250k, pyruvate carboxylase deficiency

• Variable phenotype with most common being infantile severe onset

• Mild to moderate presents with hyperammonemia, proline, alanine

Fumarase Deficiency

• Very rare AR condition

• Severe infantile onset encephalopathy

• Het variants in FH cause hereditary leiomyomatosis

• Renal cell carcinoma

mtDNA depletion disorders

• Variants in nuclear genes lead to changes in mitochondrial synthesis or mtDNA replication

• Most are AR

Symptoms include

• Lactic acidosis and encephalopathy

• Leigh syndrome

• Developmental delay and myopathy

• Seizure, renal failure, liver failure

• Sensorineural and retinal dystrophy

Kearnes Sayre Syndrome

Most severe mtDNA depletion disorder, Clinical triad <20yrs:

•Progressive opthalmoplegia

•Pigmentary retinopathy

•Heart block

Other symptoms

•Cerebellar ataxia

•Seizures

•Intellectual disability

•Dementia

•Kidney disease

•Myopathy

•Poor growth

•Cardiomyopathy or conduction defect

•Endocrine dysfunction

•GI dysmotility

Pearson Syndrome

Moderately severe mtDNA disorder Before 1yr:

•Pancytopenia and sideroblastic anemia that spontaneously resolve in first few years of life

•Pancreatic dysfunction

•Lactic acidosis

•High mortality in early childhood

Other symptoms

•Poor growth

•Kidney disease

•Hypotonia

•Cardiac dysfunction

•May progress to KSS phenotype)

Chronic Progressive Ophthalmoplegia (CPEO)

Least severe mtDNA depletion disorder, Adolescence to adult onset:

•Ptosis

•Ophthalmoplegia (extraocular muscle paralysis)

CPEO-Plus

•Exercise intolerance

•Myopathy

•Dysphagia

Life expectancy is typically normal.

mtDNA mutation conditions

highly variable involving a range of mutations in the mtDNA

MERRF

Myoclonic Epilepsy with Ragged Red Fibers

• Childhood to adolescence onset myoclonus (involuntary muscle contractions) and generalized seizures

MNGIE

Mitochondrial NeuroGastroIntestinal Encephalomyopathy

MIDD

Maternally lnherited Diabetes and Deafness

NARP

Neuropathy, Ataxia, Retinitis Pigmentosa