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Differential diagnosis of AADC deficiency: Mitochondrial disorders

What are mitochondrial disorders?

  • Mitochondrial disorders are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain1
  • The estimated prevalence of mitochondrial disorders was found to be at least 20 per 100,000 in the population2

Types of mitochondrial disorders

Common clinical features of mitochondrial disorders include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy and diabetes mellitus.1

Mitochondrial disorders and their primary clinical features:1

Mitochondrial disorderPrimary clinical features
Alpers-Huttenlocher syndrome
  • Hypotonia
  • Seizures
  • Liver failure
ANS (including SANDO and MEMSA*)
  • Other ANS: Sensory axonal neuropathy with variable sensory and cerebellar ataxia
  • External ophthalmoplegia
  • Bilateral ptosis
  • Progressive external ophthalmoplegia onset at age <20 years
  • Pigmentary retinopathy
  • One of the following: CSF protein >1 g/L, cerebellar ataxia, heart block
Pearson syndrome
  • Sideroblastic anaemia of childhood
  • Pancytopenia
  • Exocrine pancreatic failure
LIMM (fatal and non-fatal forms)
  • Hypotonia in first year of life
  • Feeding and respiratory difficulties
Leigh syndrome
  • Subacute relapsing encephalopathy
  • Cerebellar and brain stem signs
  • Infantile onset
  • Late childhood- or adult-onset peripheral neuropathy
  • Ataxia
  • Pigmentary retinopathy
  • Stroke-like episodes at age <40 years
  • Seizures and/or dementia
  • Ragged-red fibres and/or lactic acidosis
  • Myopathy
  • Seizures
  • Cerebellar ataxia
  • Myoclonus
  • Seizures
  • Cerebellar ataxia
  • Myopathy
  • Subacute painless bilateral visual failure
  • Males: females ~4:1
  • Median age of onset: 24 years
*Also referred to as MIRAS and SCAE.

Overlapping and differentiating symptoms of mitochondrial disorders and AADC deficiency

  • In infants, clinical features such as hypokinetic rigid syndrome and generalised dystonia can mimic those seen in AADC deficiency and other paediatric neurotransmitter disorders, making diagnosis difficult based on clinical presentation alone3
  • The presence of oculogyric crises may help to differentiate AADC deficiency from a mitochondrial disorder, however, this is not sufficient to make a definitive diagnosis as although it is not typical, oculogyric crises may sometimes present in mitochondrial disorders4
  • Therefore, molecular genetic testing is warranted to confirm or rule out a diagnosis of AADC deficiency5

Overlapping and differentiating symptoms of mitochondrial disorders and AADC deficiency:

*Seizures are uncommon in AADC deficiency but have been reported.
While oculogyric crisis has been reported, it is not typical of mitochondrial disorders.

AADC, aromatic L-amino acid decarboxylase; ANS, ataxia neuropathy syndrome; CSF, cerebrospinal fluid; CPEO, chronic progressive external ophthalmoplegia; KSS, Kearns-Sayre syndrome; LIMM, lethal infantile mitochondrial myopathy; LHON, Leber’s hereditary optic neuropathy; MELAS, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; MEMSA, myoclonic epilepsy myopathy sensory ataxia; MERRF, myoclonic epilepsy with ragged-red fibres; MIRAS, mitochondrial recessive ataxia syndrome; NARP, neurogenic weakness with ataxia and retinitis pigmentosa; SANDO, sensory ataxic neuropathy, dysarthria, ophthalmoplegia; SCAE, spinocerebellar ataxia with epilepsy.
  1. Adam MP, Ardinger HH, Pagon RA, et al (Editors). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020.
  2. Schaefer AM, et al. BBA. 2004;1659:115–120.
  3. Marecos C, Ng J, Kurian MA. J Inherit Metab Dis. 2014;37:619–626.
  4. Garcia-Cazorla A, et al. Mitochondrion. 2008;8:273–278.
  5. Wassenberg T, et al. Orphanet J Rare Dis. 2017;12:12.
  6. Garcia-Cazorla A, et al. Mitochondrion. 2008;8:273–278.
  7. Ng J, et al. Nat Rev Neurol. 2015;11:567–584.
  8. Manegold C, et al. J Inherit Metab Dis. 2009;32:371–380.
  9. Gropman AL. Neurotherapeutics. 2013;10:273–285.

Welcome to AADC Insights

A website for healthcare professionals, provided by PTC Therapeutics

This educational website provides information to support the early and accurate diagnosis of rare neurotransmitter disorders, including AADC deficiency

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