Combined oxidative phosphorylation defect type 23

What it is

From: Orphanet

A rare mitochondrial disease characterized by early onset of hypertrophic cardiomyopathy and variable neurologic symptoms including global developmental delay, hypotonia, intellectual disability, visual impairment, and seizures. Lactic acidosis is present in all patients. Muscle biopsy usually shows decreased activity of mitochondrial complexes I and IV. Brain imaging may reveal variable abnormal signal intensities in the thalamus, basal ganglia, and/or brain stem.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hypertrophic cardiomyopathy · Very frequent (99-80%)

Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.

Lactic acidosis · Very frequent (99-80%)

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

Abnormality of the nervous system · Frequent (79-30%)

An abnormality of the nervous system.

Floppy infant · Frequent (79-30%)

Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).

Abnormal basal ganglia MRI signal intensity · Occasional (29-5%)

A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia.

Abnormal brainstem MRI signal intensity · Occasional (29-5%)

A deviation from normal signal on magnetic resonance imaging (MRI) of the brainstem.

Abnormal thalamic MRI signal intensity · Occasional (29-5%)

A deviation from normal signal on magnetic resonance imaging (MRI) of the thalamus.

Cognitive impairment · Occasional (29-5%)

Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.

Congestive heart failure · Occasional (29-5%)

The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.

Cyanosis · Occasional (29-5%)

Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.

Decreased activity of mitochondrial complex I · Occasional (29-5%)

A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.

Decreased activity of mitochondrial complex IV · Occasional (29-5%)

A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria.

Easy fatigability · Occasional (29-5%)

Increased susceptibility to fatigue.

Failure to thrive · Occasional (29-5%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Other findings in the same source

From: Orphanet

Additional reported features include Feeding difficulties in infancy (Occasional (29-5%)); Global developmental delay (Occasional (29-5%)); Intellectual disability, mild (Occasional (29-5%)); Left ventricular hypertrophy (Occasional (29-5%)); Leukodystrophy (Occasional (29-5%)); Paroxysmal dyspnea (Occasional (29-5%)); Respiratory failure (Occasional (29-5%)); Right ventricular hypertrophy (Occasional (29-5%)); Seizure (Occasional (29-5%)); Severely reduced ejection fraction (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood; Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 11.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Combined oxidative phosphorylation defect type 23 is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Combined oxidative phosphorylation defect type 23. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.