Differential diagnosis of AADC deficiency: Mitochondrial disorders

DIAGNOSIS & TESTING > Differential diagnosis of AADC deficiency > Differential diagnosis of AADC deficiency: Mitochondrial disorders

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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 disorder	Primary clinical features
Alpers-Huttenlocher syndrome	Hypotonia Seizures Liver failure
ANS (including SANDO and MEMSA*)	SANDO Other ANS: Sensory axonal neuropathy with variable sensory and cerebellar ataxia
CPEO	External ophthalmoplegia Bilateral ptosis
KSS	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
NARP	Late childhood- or adult-onset peripheral neuropathy Ataxia Pigmentary retinopathy
MELAS	Stroke-like episodes at age <40 years Seizures and/or dementia Ragged-red fibres and/or lactic acidosis
MEMSA*	Myopathy Seizures Cerebellar ataxia
MERRF	Myoclonus Seizures Cerebellar ataxia Myopathy
LHON	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.

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GL-AADC-1028 | April 2022